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Vitamin D: Modulator of the immune system

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Vitamin D: Modulator of the immune system

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Abstract

1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), the active form of vitamin D, is known to regulate calcium and phosphorus metabolism, thus being a key-player in bone-formation. However 1,25(OH)(2)D(3) also has a physiological role beyond its well-known role in skeletal homeostasis. Here, we describe 1,25(OH)(2)D(3) as an immunomodulator targeting various immune cells, including monocytes, macrophages, dendritic cells (DCs), as well as T-lymphocytes and B-lymphocytes, hence modulating both innate and adaptive immune responses. Besides being targets, immune cells express vitamin D-activating enzymes, allowing local conversion of inactive vitamin D into 1,25(OH)(2)D(3) within the immune system. Taken together, these data indicate that 1,25(OH)(2)D(3) plays a role in maintenance of immune homeostasis. Several epidemiological studies have linked inadequate vitamin D levels to a higher susceptibility of immune-mediated disorders, including chronic infections and autoimmune diseases. This review will discuss the complex immune-regulatory effects of 1,25(OH)(2)D(3) on immune cells as well as its role in infectious and autoimmune diseases, more in particular in tuberculosis and type 1 diabetes (T1D).

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... For about 30 years, a complicated interaction has been described between neuroinflammation, immune activation and modifications in brain circuits associated to depression and anxiety [34]. Therefore, vitamin D is known for regulation of innate immunity, both as a transcription and growth factor by interrelating with surface receptors in diverse immune cells [5]. Vitamin D is, therefore, associated with its ability to regulate both immune responses of peripheral and central nervous systems [46]. ...
... The antimicrobial properties of vitamin D has been described as its first immune-related properties, but it is also involved in the modulation of both innate and adaptive immune reactions [5]. In this perspective, depression and anxiety are often related with a low-grade inflammatory significance and peripheral increase in acute-phase proteins and inflammatory cytokines [17]. ...
... Vitamin D has numerous effects on the CNS to act as mood modulator, apart from the wide distribution of vitamin D receptors in brain regions closely implicated in depression and anxiety disorders pathophysiology. Though, further studies are required to clarify the mechanisms associated with mood improvement and to find out the groups of patients who might be benefited from vitamin D supplementation [5]. ...
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Background Vitamin D can influence more than 200 genes in various tissues showing its credibility among the fat-soluble vitamins. Vitamin D deficiency is directly proportional to major clinical conditions such as cardiovascular diseases, diabetes, malignancy, and multiple sclerosis. This study was conducted to determine the vitamin D level of individuals and its association with depression. Methods Vitamin D levels of 100 healthy and 100 depressed subjects were determined. The isolated subjects were screened on the Beck Depression Inventory (BDI) scale and divided into three groups according to their age. Group-I comprised subjects of age 20 years and below, Group-II included subjects of age 21 to 60, and Group-III comprised subjects of ≥ 61 years of age. A sufficient level of vitamin D in normal subjects was noted, while mild deficiency of vitamin D status was observed in depressed subjects. Results Our study has reported a higher percentage of vitamin D deficiency in the Peshawar region. The results of our study indicated that depression was common in individuals having vitamin D deficiency. Conclusions The study showed a very high frequency of vitamin D deficiency in subjects with depression in Peshawar, Pakistan. The deficiency of vitamin D was observed more in females as compared to males. Further studies should explicate whether the highly widespread vitamin D deficiency could be cost-effectively treated as part of preventive or treatment interventions for depression.
... Next, 25-hydroxyvitamin D3 is hydroxylated in the kidneys by cytochrome P450 Family 27 Subfamily B Member 1 (CYP27B1) resulting in the active form of vitamin D, i.e. 1,25-dihydroxyvitamin D3 (calcitriol). 1,25-dihydroxyvitamin D3 binds and activates the vitamin D receptor (VDR) through which it regulates gene expression (Ascherio, et al., 2010;Baeke, et al., 2010). Excessive vitamin D signalling is prevented by the induction of 24-hydroxylase cytochrome P450 family 24 subfamily A member 1 (CYP24A1) and the amount of circulating 1,25-dihydroxyvitamin D3 is regulated by renal CYP27B1 activity (Baeke, et al., 2010). ...
... 1,25-dihydroxyvitamin D3 binds and activates the vitamin D receptor (VDR) through which it regulates gene expression (Ascherio, et al., 2010;Baeke, et al., 2010). Excessive vitamin D signalling is prevented by the induction of 24-hydroxylase cytochrome P450 family 24 subfamily A member 1 (CYP24A1) and the amount of circulating 1,25-dihydroxyvitamin D3 is regulated by renal CYP27B1 activity (Baeke, et al., 2010). Besides from UV-mediated synthesis, vitamin D can also be obtained from diet. ...
... However, the largest source of vitamin D3 is that produced upon sunlight exposure (Baeke, et al., 2010). Levels of 25-hydroxyvitamin D3 reflect both the production by sun exposure as well as dietary uptake. ...
... Circulating 25(OH)D forms a complex with vitamin D-binding protein (DBP) and reaches target cells, such as immune cells. CYP27B1 in the target cells hydroxylates 25(OH)D to 1,25(OH) 2 D [2]. The latter maintains the balance between Tregs and effector T cells by increasing the number of Tregs and reducing that of T helper 1 (Th1) cells and Th17 cells, diminishes memory B-cell counts and antibody levels, and inhibits the expression of some inflammatory factors [1]. ...
... CYP27B1 is expressed in immune cells and hydroxylates 25(OH)D to 1,25(OH) 2 D, and the latter plays an immunological part [2]. The mRNA expression of CYP27B1 in PBMCs was lower in SLE patients than in HCs (p < 0.001) as shown in Figure 1. ...
Article
Background/aim: To measure the expression of 1α-hydroxylase (CYP27B1) and serum 25(OH)D concentration in systemic lupus erythematosus (SLE) and to investigate the role of CYP27B1 in SLE. Materials and methods: Seventy-seven SLE patients and 35 healthy controls (HCs) were enrolled from September 2017 to January 2020. The study design is cross-sectional. mRNA expression of CYP27B1 in peripheral blood mononuclear cells (PBMCs) was measured by reverse-transcription quantitative PCR, the protein level of CYP27B1 was quantified by western blotting, and the serum level of 25(OH) D was determined by an enzyme-linked immunosorbent assay. Results: The mRNA expression of CYP27B1 in PBMCs was significantly lower in SLE patients than in HCs (p < 0.001), and the protein quantification confirmed that CYP27B1 expression was lower in SLE patients than in HCs (p = 0.001). Among SLE patients, the prevalence of lupus nephritis was higher in a subgroup with lower CYP27B1 mRNA expression than in a subgroup with normal CYP27B1 mRNA expression (41.07% vs. 14.28%, p = 0.028). The mRNA expression of CYP27B1 negatively correlated with the Systemic Lupus Erythematosus Disease Activity Index (r = −0.331, p = 0.003). Serum 25(OH)D concentration was lower in SLE patients than in HCs (37.64 ± 19.89 vs. 50.58 ± 12.74 ng/mL, mean ± SD, p = 0.003). Conclusion: The expression of CYP27B1 in PBMCs may be related to SLE pathogenesis, disease activity, and nephritis.
... Modulating immune responses in the endometrium and decidua may be the focus of future therapeutic approaches in URPL. For example, the impact of seminal plasma on the expansion of Tregs may provide a novel therapeutic intervention that has already been used in assisted reproductive technologies [92][93][94]. TGF-β is a major component of seminal plasma that plays a role in regulating the maternal immune response [92]. According to our findings, levels of TGF-β in cervicovaginal fluid were lower in women with URPL compared to the control group. ...
... For example, the impact of seminal plasma on the expansion of Tregs may provide a novel therapeutic intervention that has already been used in assisted reproductive technologies [92][93][94]. TGF-β is a major component of seminal plasma that plays a role in regulating the maternal immune response [92]. According to our findings, levels of TGF-β in cervicovaginal fluid were lower in women with URPL compared to the control group. ...
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Background and aim: The Th17/Treg balance in peripheral blood and reproductive tissues may have a role in the etiology of unexplained recurrent pregnancy loss (URPL). In this study, we evaluated the major cytokine of Treg cells transforming growth factor-beta (TGF-β), and their specific transcription factor Forkhead box P3 (FOXP3), as well as the most highlighted cytokine of Th17 cells (interleukin [IL]-17A) in both URPL patients and healthy women. Methods: Samples were extracted from the peripheral blood, endocervix, endometrium, and vagina of 14 patients with URPL and 12 normal non-pregnant women as a control (normal) group. Quantitative reverse transcription polymerase chain reaction was used to determine gene expression. Enzyme-linked immunosorbent assay was used to determine the levels of cytokines in the serum and cervicovaginal fluid. Results: We found that in the URPL group, FOXP3 gene expression was considerably higher in peripheral blood than in the normal group (P=0.043). TGF-β levels in the cervicovaginal fluid were different in the URPL and normal groups (P=0.015). In comparison to the control group, women with URPL had significantly greater IL-17 gene expression in the peripheral blood (P=0.01). Conclusion: Lower TGF-β levels in the cervicovaginal fluid of patients compared to controls may be related with increased IL-17 and FOXP3 mRNA levels in patients with URPL. Dysregulation of local immune responses in reproductive tissues may represent dysregulation of systemic regulatory immunological responses in the pathogenesis of URPL. Relevance for patients: Dysregulation of immune responses may play a role in the pathogenesis of URPL at least in some patients with URPL. We conclude that the breakdown of tolerance in the local immune responses is more critical than the breakdown of tolerance in systemic tolerance in the pathogenesis of URPL. Therefore, modulating immune responses in the endometrium and decidua may be the focus of future therapeutic approaches in URPL. The impact of seminal plasma on the expansion of Tregs may provide a novel therapeutic intervention that has already been used in assisted reproductive technologies. Therefore, we suggest that transvaginal TGF-β in women with URPL may induce maternal tolerance which leads to the successful pregnancy.
... In line with this, several studies have suggested an inverse association between serum vitamin D levels and symptoms related to depression and anxiety [46][47][48]. In addition to glial cells, VDRs and CYP27B1 are also expressed in several other immune cells, such as CD4 + and CD8 + T cells, B cells, macrophages, neutrophils, and dendritic cells [49]. Notably, it has been shown that calcitriol is capable of modulating innate and adaptive immune responses [49]. ...
... In addition to glial cells, VDRs and CYP27B1 are also expressed in several other immune cells, such as CD4 + and CD8 + T cells, B cells, macrophages, neutrophils, and dendritic cells [49]. Notably, it has been shown that calcitriol is capable of modulating innate and adaptive immune responses [49]. Furthermore, the positive modulation of antioxidant enzymes by calcitriol is known to contribute to redox homeostasis and, consequently, to the attenuation of the neuroinflammatory process [50,51]. ...
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Major depressive disorder and anxiety disorders are common and disabling conditions that affect millions of people worldwide. Despite being different disorders, symptoms of depression and anxiety frequently overlap in individuals, making them difficult to diagnose and treat adequately. Therefore, compounds capable of exerting beneficial effects against both disorders are of special interest. Noteworthily, vitamin D deficiency has been associated with an increased risk of developing depression and anxiety, and individuals with these psychiatric conditions have low serum levels of this vitamin. Indeed, in the last few years, vitamin D has gained attention for its many functions that go beyond its effects on calcium–phosphorus metabolism. Particularly, antioxidant, anti-inflammatory, pro-neurogenic, and neuromodulatory properties seem to contribute to its antidepressant and anxiolytic effects. Therefore, in this review, we highlight the main mechanisms that may underlie the potential antidepressant and anxiolytic effects of vitamin D. In addition, we discuss preclinical and clinical studies that support the therapeutic potential of this vitamin for the management of these disorders.
... Vitamin D deficiency is associated with higher concentrations of CRP and IL-6 42,43 . Therefore, COVID-19 patients with vitamin D deficiency may provide a greater inflammatory response that is positively associated with mortality risk 44 . ...
... Therefore, a significant change occurs in the adaptive immune response from Th1 to a more regulatory Th2 response that increases the production of Th2 associated cytokines 45 . Moreover, vitamin D can increase the expression of angiotensin-converting enzyme-2 (ACE-2) and suppress the angiotensin-renin system and angiotensin II production, which is a pro-inflammatory biomarker 42,46 . As result, these processes may attenuate the cytokine storm perpetuating a pro-inflammatory state and worsening severe outcomes of COVID-19. ...
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Background and aim Data on the associations of vitamin D levels with severe outcomes of coronavirus disease 2019 (COVID-19) among critically ill elderly patients are not conclusive and also no information is available about some outcomes such as delirium. Therefore, the current study was done to assess these associations in critically ill elderly COVID-19 patients. Methods In total, 310 critically ill COVID-19 patients, aged ≥65 years, were included in the current single center prospective study. All patients were hospitalized in the intensive care unit (ICU). We collected data on demographic characteristics, laboratory parameters, blood pressure, comorbidities, medications, and types of mechanical ventilation at baseline (the first day of ICU admission). Patients were categorized based on serum 25(OH)D3 levels at the baseline [normal levels (>30 ng/mL), insufficiency (20-30 ng/mL), deficiency (<20 ng/mL)]. Data on delirium incidence, mortality, invasive mechanical ventilation (IMV) requirement during treatment, length of ICU and hospital admission, and re-hospitalization were recorded until 45 days after the baseline. Results Vitamin D deficiency and insufficiency were prevalent among 12% and 37% of study participants, respectively. In terms of baseline differences, patients with vitamin D deficiency were more likely to be older, have organ failure, take propofol, need IMV, and were less likely to need face mask compared to patients with normal levels of vitamin D. A significant positive association was found between vitamin D deficiency and risk of delirium. After controlling for potential confounders, patients with vitamin D deficiency had a 54% higher risk of delirium compared to those with vitamin D sufficiency (HR: 1.54, 95% CI: 1.02-2.33). Such a positive association was also seen for 45-day COVID-19 mortality (HR: 3.95, 95% CI: 1.80-8.67). Also, each 10 ng/mL increase in vitamin D levels was associated with a 45% and 26% lower risk of 45-day mortality (HR: 0.55, 95% CI: 0.40-0.74) and ICU mortality due to COVID-19 (HR: 0.74, 95% CI: 0.60-0.92), respectively. In terms of other COVID-19 outcomes including IMV requirement during treatment, prolonged hospitalization, and re-hospitalization, we found no significant association in relation to serum 25(OH)D3 levels either in crude or fully adjusted models. Conclusion Vitamin D deficiency was associated with an increased risk of delirium and mortality among critically ill elderly COVID-19 patients.
... Vitamin D is essential for normal bone development and mineralization through the regulation of calcium and phosphorus homeostasis. In addition, vitamin D also exhibits many non-sceletal effects [7,8,9,10]. Recent evidence suggests that vitamin D plays a role in a variety of immunologic processes such as modulation of inflammatory pathways and susceptibility to infections manifesting antibacterial, antiviral and anti-inflammatory effects [7,8,9]. ...
... In addition, vitamin D also exhibits many non-sceletal effects [7,8,9,10]. Recent evidence suggests that vitamin D plays a role in a variety of immunologic processes such as modulation of inflammatory pathways and susceptibility to infections manifesting antibacterial, antiviral and anti-inflammatory effects [7,8,9]. Vitamin D deficiency has been linked to increased risk or severity of viral infections, including Covid-19 [10,11]. ...
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Introduction: Results from several studies indicated that vitamin D plays a role in a variety of immunologic processes such as modulation of inflammatory pathways and susceptibility to infections. Aim of the study: To assess the effects of vitamin D supplementation on bacterial exacerbations in patients with severe chronic obstructive pulmonary disease (COPD) with low vitamin D serum level. Methods: We performed an observational, non-randomized, open-label study including 36 patients with severe COPD who besides the recommended chronic treatment for stable disease took oral vitamin D supplementation in dose of 2000 IU daily during a six month-period (Group 1). In addition, 35 patients with severe COPD, matched to the study subjects of the Group 1 by sex, age and serum vitamin D level, who did not receive vitamin D supplementation served as controls (Group 2). Analysis of exacerbations, including their incidence and duration, as well as incidence of relapses and duration of exacerbation-free interval, was done for each study subjects based on daily diary cards maintained by all of them during the mentioned period. Results: Mean serum vitamin D levels at baseline did not differ significantly between examined groups (21.7 vs. 22.1; P = 0.457). At the end of the study its mean level was significantly higher in the Group 1 as compared to Group 2 (30.1 vs. 23.4; P = 0.000). Mean number of the first exacerbation over a six month-period was significantly lower in the Group 1 as compared to their mean number in the Group 2 (0.8 vs. 0.9; P = 0.001). Mean duration of the first exacerbation in the Group 1 (6.7 ± 1.2 days) was significantly lower as compared to its mean duration in the Group 2 (7.2 ± 1.3 days) (P = 0.033). Mean number of relapses registered in the Group 1 (0.2 ± 0.1) was significantly lower than its mean number registered in the Group 2 (0.4 ± 0.2) (P = 0.000). Mean exacerbation-free interval in the Group 1 (39.3 ± 10.1 days) was significantly longer than in the Group 2 (33.7 ± 11.8 days) (P = 0.052). Conclusion: Our findings indicated that vitamin D supplementation may impact the incidence and duration of bacterial exacerbations in patients with COPD. There is a need of further studies to elucidate the role of vitamin D supplementation on the course of COPD.
... Vitamin D is essential for normal bone development and mineralization through the regulation of calcium and phosphorus homeostasis. In addition, vitamin D also exhibits many non-sceletal effects [7,8,9,10]. Recent evidence suggests that vitamin D plays a role in a variety of immunologic processes such as modulation of inflammatory pathways and susceptibility to infections manifesting antibacterial, antiviral and anti-inflammatory effects [7,8,9]. ...
... In addition, vitamin D also exhibits many non-sceletal effects [7,8,9,10]. Recent evidence suggests that vitamin D plays a role in a variety of immunologic processes such as modulation of inflammatory pathways and susceptibility to infections manifesting antibacterial, antiviral and anti-inflammatory effects [7,8,9]. Vitamin D deficiency has been linked to increased risk or severity of viral infections, including Covid-19 [10,11]. ...
Article
Full-text available
Introduction: Results from several studies indicated that vitamin D plays a role in a variety of immunologic processes such as modulation of inflammatory pathways and susceptibility to infections. Aim of the study: To assess the effects of vitamin D supplementation on bacterial exacerbations in patients with severe chronic obstructive pulmonary disease (COPD) with low vitamin D serum level. Methods: We performed an observational, non-randomized, open-label study including 36 patients with severe COPD who besides the recommended chronic treatment for stable disease took oral vitamin D supplementation in dose of 2000 IU daily during a six month-period (Group 1). In addition, 35 patients with severe COPD, matched to the study subjects of the Group 1 by sex, age and serum vitamin D level, who did not receive vitamin D supplementation served as controls (Group 2). Analysis of exacerbations, including their incidence and duration, as well as incidence of relapses and duration of exacerbation-free interval, was done for each study subjects based on daily diary cards maintained by all of them during the mentioned period. Results: Mean serum vitamin D levels at baseline did not differ significantly between examined groups (21.7 vs. 22.1; P = 0.457). At the end of the study its mean level was significantly higher in the Group 1 as compared to Group 2 (30.1 vs. 23.4; P = 0.000). Mean number of the first exacerbation over a six month-period was significantly lower in the Group 1 as compared to their mean number in the Group 2 (0.8 vs. 0.9; P = 0.001). Mean duration of the first exacerbation in the Group 1 (6.7 ± 1.2 days) was significantly lower as compared to its mean duration in the Group 2 (7.2 ± 1.3 days) (P = 0.033). Mean number of relapses registered in the Group 1 (0.2 ± 0.1) was significantly lower than its mean number registered in the Group 2 (0.4 ± 0.2) (P = 0.000). Mean exacerbation-free interval in the Group 1 (39.3 ± 10.1 days) was significantly longer than in the Group 2 (33.7 ± 11.8 days) (P = 0.052). Conclusion: Our findings indicated that vitamin D supplementation may impact the incidence and duration of bacterial exacerbations in patients with COPD. There is a need of further studies to elucidate the role of vitamin D supplementation on the course of COPD.
... The consensus is that vertebrates have been living with symbiotic intestinal helminths for at least 100-200 million years, but such symbiosis could go back 400 million Unknown Improved fatigue [56] Ketogenic diet muciniphila " Bifidobacterium # Faecalibacterium spp. # [133][134][135] Normalized MS gut microbiome [46] Unknown No clinical benefit [136] Improved fatigue [137] Improved inflammatory status [58,138] Decreased EDSS [58] Biotin supplement L. murinus " [139] Protection against hypoxia [61] Improvement in spinal cord [61] Slowed EDSS progression [62] Vitamin D supplement Prevotella l Bifidobacterium # [140] Treg " Th1/Th17 # [141] Lower disease progression in vitamin D insufficient patients [64] No benefit of high-dose over lowdose [142] Summary of changes due to nutritional interventions as compared to control groups. Articles were collected through Google Scholar, PubMed, Web of Science, clinicaltrials.gov ...
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Multiple sclerosis (MS), a neurological autoimmune disorder, has recently been linked to neuro-inflammatory influences from the gut. In this review, we address the idea that evolutionary mismatches could affect the pathogenesis of MS via the gut microbiota. The evolution of symbiosis as well as the recent introduction of evolutionary mismatches is considered, and evidence regarding the impact of diet on the MS-associated microbiota is evaluated. Distinctive microbial community compositions associated with the gut microbiota of MS patients are difficult to identify, and substantial study-to-study variation and even larger variations between individual profiles of MS patients are observed. Furthermore, although some dietary changes impact the progression of MS, MS-associated features of microbiota were found to be not necessarily associated with diet per se. In addition, immune function in MS patients potentially drives changes in microbial composition directly, in at least some individuals. Finally, assessment of evolutionary histories of animals with their gut symbionts suggests that the impact of evolutionary mismatch on the microbiota is less concerning than mismatches affecting helminths and protists. These observations suggest that the benefits of an anti-inflammatory diet for patients with MS may not be mediated by the microbiota per se. Furthermore, any alteration of the microbiota found in association with MS may be an effect rather than a cause. This conclusion is consistent with other studies indicating that a loss of complex eukaryotic symbionts, including helminths and protists, is a pivotal evolutionary mismatch that potentiates the increased prevalence of autoimmunity within a population.
... Different metabolites of vitamin D can be included in production animal diets. Dietary vitamin D is supplied in poultry diets as vitamin D 3 or as a combination of D 3 and 25-hydroxyvitamin D 3 ( 25 OHD3), a hydroxylated form of vitamin D 3 and major circulating vitamin D metabolite (17). The presence of the vitamin D receptor in cells unrelated to mineral metabolism suggests that vitamin D plays an important role in more tissues (18). ...
Article
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Vitamin D signaling is important for intestinal homeostasis. An increase in vitamin D receptors in immune cells can modulate cell phenotype and cytokine secretion. Cytokines regulate both pro- (interleukin 17; IL-17) and anti-inflammatory (IL-10) responses triggered by external stimuli. Inflammation in intestinal tissues can disrupt the structure and the remodeling of epithelial tight junction complexes, thus, compromising the protective barrier. The objective of the study was to determine the impact of dietary supplementation with 25-hydroxycholecalciferol ( 25 OHD 3 ), a hydroxylated metabolite of vitamin D, on intestinal cytokine abundance and epithelial barrier integrity over time in broilers. A randomized complete block design experiment was conducted to evaluate the effect of dietary 25 OHD 3 inclusion on relative protein expression of the cytokines, IL-17 and IL-10, and tight junction proteins, Zona Occludens 1 (ZO-1), and Claudin-1 (CLD-1), in broiler chicken duodenum and ileum from 3 to 21 days post-hatch. On day 0, male chicks ( n = 168) were randomly assigned to raised floor pens. Experimental corn–soybean meal-based treatments were as follows: (1) a common starter diet containing 5,000 IU of D 3 per kg of feed (VITD 3 ) and (2) a common starter diet containing 2,240 IU of D 3 + 2,760 IU of 25 OHD 3 per kg of feed ( 25 OHD 3 ) fed from days 0 to 21. On days 3, 6, 9, 12, 15, 18, and 21, 12 birds per treatment were euthanized to collect tissue samples for quantitative, multiplex, and fluorescent Western blot analysis. Target proteins were quantified using Image Quant TL 8.1 and expressed relative to total protein. Feeding 25 OHD 3 post-hatch decreased ileal IL-10 (anti-inflammatory) protein expression in 21-day-old broilers compared with VITD 3 only ( P = 0.0190). Broilers fed only VITD 3 post-hatch had greater IL-17 (pro-inflammatory) protein expression in the ileum at 18 and 21 days-of-age ( P = 0.0412) than those that fed 25 OHD 3 . Dietary inclusion of 25 OHD 3 lowered the abundance of key inflammatory cytokines in the ileum of young broilers.
... Vitamin D (Vit D) is a fat-soluble vitamin that has hormone-like actions and plays a key role in calcium and bone metabolism. The biological role of the normally active form of Vit D [1,25(OH)2D3] extends to influence various systemic processes, such as cell differentiation, immune regulation, and inflammation (Baeke et al. 2010;Labudzyns'kyĭ et al. 2014). Recently, Vit D has drawn more attention as a non-enzymatic antioxidant compound (D'Aurizio et al. 2015). ...
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This study was designed to evaluate the potential therapeutic efficacy of vitamin D (Vit D) in averting the harmful effects of type 2 diabetes mellitus (T2D). Forty male Wistar rats were allotted into four groups: (1) the control, (2) Vit D, (3) streptozotocin (STZ), and (4) STZ + Vit D groups. Rats co-treated with Vit D had significantly (p < 0.05) decreased levels of cortisol; proinflammatory cytokines, including interleukin-6 (IL-6); and malondialdehyde (MDA). Meanwhile, the levels of insulin significantly (p < 0.05) increased, whereas the activity of the antioxidant system, including glutathione (GSH), superoxide dismutase (SOD), catalase, and total antioxidant capacity (TAC), significantly (p < 0.05) decreased. Histopathological examination revealed the destruction of beta cells in the islets of Langerhans in rats with diabetes. Meanwhile, immunoexpression revealed an increase in the immunoreactivity of caspase-3 and endothelial nitric oxide synthase and a reduction in the immunoreactivity of insulin in rats with diabetes. In conclusion, Vit D ameliorated the harmful biochemical impact of diabetes mellitus, probably by increasing insulin secretion and sensitivity, ameliorating β-cell function, and decreasing cortisol levels; also, the anti-inflammatory effect of Vit D reduces the number of proinflammatory cytokines (e.g., IL-6) and increases the activity of the antioxidant system, such as GSH, SOD, TAC, and catalase while reducing lipid peroxidation enzymes (e.g., MDA).
... The inhibitory effect of the active form of vitamin D [Calcitriol (1,25 (OH) 2 D 3 )] is modulated by vitamin D receptors (VDRs) that are present in the heart, brain, pancreatic islets, immune cells, muscles and adipose tissue. These are all common target organs in the development of diabetes and its complications (20). Typically, during infection immune cells would trigger VDR signaling, to convert vitamin D to calcitriol, then induce the production of antimicrobial proteins such as cathelicidin (LL-37) via Toll-like receptor (TLR) activation (21). ...
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Patients with type-2 diabetes (T2D) are more likely to develop severe respiratory tract infections. Such susceptibility has gained increasing attention since the global spread of Coronavirus Disease 2019 (COVID-19) in early 2020. The earliest reports marked T2D as an important risk-factor for severe forms of disease and mortality across all adult age groups. Several mechanisms have been proposed for this increased susceptibility, including pre-existing immune dysfunction, a lack of metabolic flexibility due to insulin resistance, inadequate dietary quality or adverse interactions with antidiabetic treatments or common comorbidities. Some mechanisms that predispose patients with T2D to severe COVID-19 may indeed be shared with other previously characterized respiratory tract infections. Accordingly, in this review, we give an overview of response to Influenza A virus and to Mycobacterium tuberculosis (Mtb) infections. Similar risk factors and mechanisms are discussed between the two conditions and in the case of COVID-19. Lastly, we address emerging approaches to address research needs in infection and metabolic disease, and perspectives with regards to deployment or repositioning of metabolically active therapeutics.
... Vitamin D, which was previously known to be involved only in calcium homeostasis, is now known to have several other functions in the human body [22]. Subclinical and asymptomatic vitamin D deficiency is associated with increased risk of multiple malignancies, metabolic and cardiovascular diseases, diabetes, and immune disorders [23]. Studies regarding vitamin D supplementation in African populations are limited [24,25]. ...
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Vitamin D reportedly plays an important role in the pathogenesis of diabetes mellitus; however, this role is unclear and debated. This study investigated the association between 25 (OH) vitamin D, vitamin D-binding proteins, and vitamin D receptor (VDR) polymorphisms in healthy individuals and those with prediabetes and type 2 diabetes mellitus (T2D) from South Africa. A cross-sectional study was conducted involving subjects of mixed ancestry aged ≥20 years. Males presented with higher mean 25 (OH) vitamin D levels than females, while females exhibited significantly higher serum vitamin D-binding protein levels. Significant differences in mean 25 (OH) vitamin D levels were observed in normo-glycaemic, prediabetes, screen-detected DM, and known DM individuals. Vitamin D receptor SNPs Fok1 and Taq1 were not associated with glycaemic status. Fok1 was not associated with 25 (OH) vitamin D deficiency, while Taq1 was associated with vitamin D insufficiency. This study showed a high prevalence of vitamin D deficiency/insufficiency in this South African population, with decreased vitamin D levels observed in hyperglycaemic individuals, which was not linked to either vitamin D-binding protein or polymorphisms in Fok1 of the VDR gene. These results may be used as a platform for further research into diagnosis and treatment of hyperglycaemia.
... The low exposure to sunlight during summer and winter could lead to vitamin D deficiency and subsequent that leads to low innate immune response and may be increase to Mtb infection. 34,35 Conclusion There were low PTB-patients numbers in AL-Najaf Governorate in 2019 but the Youngers were the most susceptible to infected. Infection in north section was higher than south section and there were no high differences between genders. ...
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Background : pulmonary tuberculosis (PTB) is one of the most global dangerous infectious diseases worldwide, particularly in developing countries. Mycobacterium tuberculosis ( Mtb ) is the most infectious agent that caused PTB transferred by air droplets from one person to other. In the present epidemiological study, we aimed to record the total numbers and percentages of patients infected with PTB caused by Mtb during 12 months in AL-Najaf Governorate, Iraq. Methods : This study has been done in 2019 from January to the end of December in the north and south region of AL-Najaf Governorate, Iraq. Sputum of PTB-patients has been stained by Ziehl–Neelsen to Mtb diagnosis according to World Health Organization (WHO) recommendation. Results : We recorded 174 PTB-patients in AL-Najaf Governorate 2019; 89 male and 85 female; 101 and 73 in the north and south sections respectively. The age group 16-24 was the highest infected. Quarter two recorded the highest numbers of PTB-patients; 33 (60%) in the north section and 22 (40%) in the south section. Conclusion : There was low PTB incidence in AL-Najaf Governorate 2019 but the Youngers were the most susceptible to infection. Infection in the north section was higher than in the south section and there were no high differences between genders. Seasons have no high effect on the number of infections.
... Moreover, vitamin D decreases the maturation and antigen-presenting ability of dendritic cells, leading to alterations of the profiles of T helper cells (Th1, Th2, Th9, Th17) and regulatory T cells, leading to overall suppression of the adaptive immune pathway (16). Regarding B cells, vitamin D is involved in inhibition of the generation of both memory and plasma cells, as well as a reduction in immunoglobulin production by inducing apoptosis of immunoglobulin-producing B cells (17). ...
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The severity of coronavirus disease 2019 (COVID-19) is determined not only by viral damage to cells but also by the immune reaction in the host. In addition to therapeutic interventions that target the viral infection, immunoregulation may be helpful in the management of COVID-19. Vitamin D exerts effects on both innate and adaptive immunity and subsequently modulates immune responses to bacteria and viruses. Patients with chronic kidney disease (CKD) frequently have vitamin D deficiency and increased susceptibility to infection, suggesting a potential role of vitamin D in this vulnerable population. In this paper, we review the alterations of the immune system, the risk of COVID-19 infections and mechanisms of vitamin D action in the pathogenesis of COVID-19 in CKD patients. Previous studies have shown that vitamin D deficiency can affect the outcomes of COVID-19. Supplementing vitamin D during treatment may be protective against COVID-19. Future studies, including randomized control trials, are warranted to determine the effect of vitamin D supplementation on the recovery from COVID-19 in CKD patients.
... In vivo studies with VD supplementation in animals and humans have shown that VD exerts pro-mising effects on immune function, particularly in the setting of autoimmunity [22]. A prior study also proposed that VD exerts an immunomodulation effect on diverse immune cells such as monocytes, macrophages, dendritic cells (DCs), T-lymphocytes, and B-lymphocytes, hence modulating both the innate and adaptive immune responses [23]. VD plays a critical role in the body's immune system. ...
Article
Objective: To investigate the correlation of the serum vitamin A, D, and E (VA, VD, and VE) levels with the occurrence and development of recurrent respiratory tract infections (RRTIs). Methods: A total of 129 children with respiratory tract infections (RTIs) treated in our hospital from January 2018 to February 2020 (the RTIs group) and 50 healthy children undergoing physical examinations (the control group) in our hospital were recruited as the study cohort. The serum VA, VD, and VE levels were measured upon admission (the active phase) and at two weeks after discharge (the stable phase). The serum VA, VD, and VE levels in the children with RRTIs were compared with the levels in the control group, and the correlation between these three vitamins and the occurrence and development of RRTIs was analyzed. Results: The RRTIs group and the RTIs group witnessed markedly lower serum VA, VD, VE, and humoral immunity index levels, including IgG, IgA, and IgM, compared to the control group, with an apparent lower outcome in the RRTIs group than in the RTIs group. The serum levels of the above indexes in the RRTIs children were reduced in the active phase compared with the stable phase. A Pearson correlation analysis showed a positive correlation between VA and IgA. A multivariate logistic regression analysis revealed that a low BMI (Body mass index), prematurity, VA deficiency, VD deficiency, and VE deficiency were the risk factors for RRTIs in children, and outdoor activity was the protective factor. Conclusion: The VA, VD, and VE levels are closely related to RRTIs in children. It is important to determine and supplement the VA, VD, and VE levels to prevent RTIs in children.
... Not reaching this peak is an issue as bone reserves are predictive of the osteoporosis risk later in adulthood [2,3]. Vitamin D does not only act on bone tissue, it has multiple functions including immunomodulation roles of innate and adaptive responses [4]. Numerous studies have also reported a negative association between vitamin D status as measured by circulating levels of 25(OH)D and cardiovascular, infectious and some autoimmune diseases [5]. ...
Article
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Background & Aims Vitamin D is an essential micronutrient in multiple cellular and physiological regulatory processes including related bone health. Several European surveys including children and adolescents have reported a low vitamin D intake and high prevalence of insufficient or even deficient vitamin D status. In Switzerland, no recent data are available. This study aimed to assess dietary intakes, status, and major dietary sources of vitamin D in a convenience sample of Swiss healthy adolescents. Methods Adolescents aged between 11 and 18 years were recruited in the Lausanne region, Switzerland, between April and November 2017. Their diet was assessed using two 24-hour recalls. Vitamin D content of consumed foods was calculated using the Swiss Food Composition Database. Vitamin D levels were analyzed using high-performance liquid chromatography coupled with ultraviolet–visible spectroscopy. Results In 29 adolescents, median [P25-P75] vitamin D intake was 0.9 [0.6-1.5] μg/day. This value reached less than 10% of recommended intake (15 μg/day). Median plasma 25(OH)D level was 56.9 [48.3-69.8] nmol/L. One-third of participants had therefore insufficient vitamin D status (≤50 nmol/L). Among adolescents tested in summer, 90% had a sufficient status. The main dietary sources of vitamin D were fish (35.2%) and dairy products (32.3%). Conclusion In this small group of Swiss adolescents, vitamin D intake was below the recommendations. A sufficient vitamin D level seems attainable for the majority of adolescents in summer unlike for the fall to spring period. Further studies are necessary to validate these findings on a representative sample of children and adolescent at the national level.
... 4,5 The immunomodulatory role of vitamin D in preventing autoimmune diseases by telorogenic dendritic cells induction has been widely explored. [5][6][7][8][9] Studies shows lower levels of vitamin D can lead to autoimmune diseases as autoimmune thyroid. [10][11][12] In contrast, a study assessing antithyroid peroxidase antibody (TPO-Ab) level in two categories of vitamin D; above and below 25 nmol/l of serum 25-hydroxy vitamin D [25(OH) D] found the prevalence of TPO-Ab was comparable Free Full Text Articles are Available at www.jnma.com.np between the groups. ...
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Introduction: Autoimmune thyroid disease is characterised by the generation of autoantibodies against self-antigens such as thyroid peroxidase, thyroglobulin, and thyroid-stimulating hormone receptor. Recent studies have implicated the role of hypovitaminosis D to immune dysfunction, failure of self-tolerance and generation of autoantibodies. This study aimed to find out the prevalence of autoimmune thyroid disease among hypovitaminosis D patients in a tertiary care centre. Methods: A descriptive cross-sectional study was conducted among participants between the ages of 18 years to 65 years who visited the Department of Biochemistry of a tertiary care centre between the periods of July 2018 to December 2019. The study was initiated after receiving ethical approval from the Institutional Review Committee (Reference number: 42,8/074/075-IRC). Data was collected using a self-administered questionnaire followed by anthropometric measurement and blood collection. Thyroid hormone, thyroid peroxidase antibody and 25-hydroxy vitamin D were measured by chemiluminescence technique. Convenience sampling was used. Point estimate and 95% Confidence Interval were calculated. Results: Among 83 patients, 39 (46.98%) (42.32–51.63, 95% Confidence Interval) had autoimmune thyroid disease. Conclusions: The prevalence of autoimmune thyroid disease among patients with hypovitaminosis D was similar to studies conducted in comparable settings.
... Recently, some studies have shown that 1,25(OH)2D regulates both adaptive and innate immunity but in opposite directions. In fact, 1,25(OH)2D inhibits the adaptive immune response and enhances the innate immune response [58]. ...
Article
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Vitamin D belongs to the group of liposoluble steroids mainly involved in bone metabolism by modulating calcium and phosphorus absorption or reabsorption at various levels, as well as parathyroid hormone production. Recent evidence has shown the extra-bone effects of vitamin D, including glucose homeostasis, cardiovascular protection, and anti-inflammatory and antiproliferative effects. This narrative review provides an overall view of vitamin D’s role in different settings, with a special focus on chronic kidney disease and kidney transplant.
... Many other tissues also express CYP27B1, including parathyroid, microglia, breast, colon, and keratinocytes, and are capable of converting 25(OH)D in circulation into the activated hormone form in an autocrine or paracrine way (10). Particularly, in such immune cells as macrophages and dendritic cells, the absence of feedback mechanisms in contrast to renal cells would instead allow the generation of high concentrations of calcitriol required for immune regulation (11). ...
Article
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Objective We conducted this study to visualize hot spots and trends in the correlation between vitamin D and immunity over the past decade with bibliometric analysis. Methods We collected relevant articles in the Web of Science Core Collection from 2012 to 2021 as the data source, and then used CiteSpace software to perform the data analysis. Some graphics were done with Graphpad software. Results A total of 1,656 articles were retrieved, with an average citation count of 25.2 times. The United States (439 articles, 26.51%) has the top number of published articles, followed by China (164 articles, 9.90%), England (135 articles, 8.15%), Italy (114 articles, 6.88%), and India (82 articles, 4.95%). The most literature is found in areas of Immunology (337 articles, 20.35%) and Biochemistry Molecular Biology (179 articles, 10.81%). In terms of institutions, the top five institutions with the highest number of publications all belong to Europe. Among them, the League of European Research Universities (LERU) (121, 7.31%) has a greater proportion of output articles. The United States Department of Health Human Services (225, 13.59%) and National Institutes of Health United States (223, 13.47%) funded most articles. The leading five authors with the largest number of publications were Hewison M (19, 1.15%), Bergman P (14, 0.85%), Agerberth B (13, 0.76%), Carlberg C (12, 0.73%), and White JH (12, 0.73%). The top five keywords with the highest co-occurrence frequency are “vitamin d” (367), “d deficiency” (217), “expression” (195), “association” (151), and “d receptor” (132). Among the 17 keyword clusters, the largest cluster is #0 “diet.” Despite cluster #13 “covid-19,” most of the clusters were conducted the studies before 2012. Conclusion The overall development of research in this field is promising. Western developed countries made outstanding contributions in this area and still take the leading role. But the participation of developing and low-income countries is also impressive. The potential therapeutic effects of vitamin D in immune-related diseases have been noted, especially in multiple sclerosis, COVID-19, etc. This is also the focus and frontier of current research. However, there is still no consensus conclusion in this field. Further research is needed in the future.
... This role was discovered 30 years ago. Previous research has revealed that our immune cells, notably macrophages and monocytes, may synthesize vitamin D on their own and boost the development of an antimicrobial protein called cathelicidin, enhancing the intracellular clearance of Mycobacterium tuberculosis [20]. In epithelia, similar processes that contribute to barrier function have been discovered. ...
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SARS-CoV-2 has affected socioeconomic activity in every country around the world since its outbreak began in 2019. 3.5 million people have died worldwide as of now, including 3.2 lakh in India. The cytokine storm significantly contributes to COVID mortality. To put it simply, the virus causes an uncontrolled release of cyto-kines, which results in severe inflammation, multi-organ failure, and death. Vitamin D was discovered to be a significant risk factor for cytokine storm in COVID patients. Numerous studies have demonstrated that those with deficient serum vitamin D levels have a significant mortality rate. The current understanding of the role of vitamin D in immune modulation in the innate and adaptive immune systems and how this may relate to COVID-19 is discussed in this article. Additionally, we evaluated the most recent clinical information about vitamin D deficiency, cytokine storm, and COVID-19 mortality.
... Consistent with the current state of knowledge, our study found that the prevalence of vitamin D deficiency and mean 25(OH) D concentrations was positively and negatively correlated with COVID-19 mortality in Africa respectively. This relationship is biologically plausible as vitamin D affects both innate and adaptive immunity which in turn increases the antiviral potential of immune cells during respiratory viral infections, including COVID-19, and may reduce poor case outcomes [29,[33][34][35][36][37][38]. In contrast, there are a number of reports that claim the link between Vitamin D and COVID-19 requires further investigation and is not yet conclusive despite seemingly strong evidence [31, 39,40]. ...
Article
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Introduction: there is a large body of literature that has linked vitamin D status in the population with COVID-19 infection risk and disease severity. However, there is paucity of evidence in African context. Hence, this study aimed to conduct an ecological analysis to explore correlation between population level vitamin D status, COVID-19 infection, and mortality in Africa. Methods: an ecological study was conducted using data from different open sources, published literatures and organizational databases. In the final analysis, we included 23 African countries which had data on prevalence of vitamin D deficiency, population level mean serum 25 (OH) D concentrations and COVID-19 data. We employed spearman correlation and linear regression. All tests were two-sided, and P- value <0.05 was considered statistically significant. Results: based on our analysis, the prevalence of vitamin D deficiency is positively correlated (r=0.6265; p= 0.0094) while mean 25(OH) D concentration is negatively correlated (r=-0.4941; p= 0.0194) with COVID-19 mortality. In addition, the median age of the national population (r=0.7015; p= 0.0003), prevalence of current use of tobacco (r=0.6071; p= 0.0075) and prevalence of obesity among adult population (r=0.7143; p= 0.0003) were positively correlated with both COVID-19 infection and mortality in Africa. Nonetheless, vitamin D status was not positively correlated with observed case fatality rate and COVID-19 infection rate. Conclusion: population vitamin D status might be related to COVID-19 mortality but not with infection rate in Africa. Due to the increasing weight of evidence that shows a link between COVID-19 and vitamin D, we strongly recommend well-designed controlled studies to explore causality and clinical trials to find out the effect of vitamin-D supplementation in the treatment and prevention of COVID-19 in African settings.
... Vitamin D supplementation was also found to enhance CD4+ T cell count in HIV infection [42]. Many studies have been done on the role of vitamin D and its balancing properties along with other supplements such as vitamin D3 in maintaining immune homeostasis [43][44][45]; well-designed randomized controlled trials are required to elucidate the plausible role of vitamin D in protective immune responses against respiratory microbes and in preventing various types of acute respiratory tract infections. ...
Article
Despite many efforts around the world to control the outbreak of COVID- 19 virus, this issue has become a pandemic. According to the latest research on the global spread of COVID- 19, researchers have found that adequate vitamin D3 increases resistance to viral infections, reduces the severity of symptoms of the disease, and ultimately mortality rate. However, the results are still contradictory. There are receptors in the human body called ACE2. The COVID- 19 virus can enter the body by binding to these receptors, and the symptoms of the disease develop gradually. Meanwhile, vitamin D3 can attach to these receptors and prevent the corona virus from attaching to the body’s organs. Thus, people who have lower levels of vitamin D3 absorbed during this epidemic should take vitamin D supplements to maintain an optimal level of 25 (OH) D in the blood. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations. There is insufficient evidence between level of vitamin D3 intake and mortality rate of COVID-19 in patients. This review summarizes some of the latest findings about the role of vitamin D3 in COVID-19 infections, severity, and mortality.
... Frontiers in Pharmacology | www.frontiersin.org July 2022 | Volume 13 | Article 863587 and increase COVID-19 severity and mortality (Rhodes et al., 2021;Seal et al., 2022;Wang et al., 2022) due to several mechanisms: first, vitamin D reduces lung permeability by modulating the renin-angiotensin system (RAS) pathway and angiotensin converting enzyme 2 (ACE2) expression; second, it promotes the production of antimicrobial peptides in the epithelium of the respiratory tract, thereby reducing the possibility of virus infection and COVID-19 symptoms; third, vitamin D favours an anti-inflammatory environment, mostly by reducing the concentration of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α and IFNγ and by increasing the expression of anti-inflammatory cytokines by macrophages; and finally, vitamin D stabilizes the physical barriers by contributing to the maintenance of functional tight junctions, gap junctions and adherence junctions (Pedersen et al., 2009;Baeke et al., 2010). On the other hand, COVID-19 is characterized by the dysregulation of the inflammatory response, especially the RAS pathway. ...
Article
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There is now sufficient evidence to support that vitamin D deficiency may predispose to SARS-CoV-2 infection and increase COVID-19 severity and mortality. It has been suggested that vitamin D3 supplementation may be used prophylactically as an affordable and safe strategy that could be added to the existing COVID-19 standard treatment. This multicenter, single-blinded, prospective randomized pilot clinical trial aimed to evaluate the safety, tolerability, and effectiveness of 10,000 IU/day in comparison with 2000 IU/day of cholecalciferol supplementation for 14 days to reduce the duration and severity of COVID-19 in 85 hospitalized individuals. The median age of the participants was 65 years (Interquartile range (IQR): 53–74), most of them (71%) were men and the mean baseline of 25-hydroxyvitamin D (25(OH)D) in serum was 15 ng/ml (standard deviation (SD):6). After 14 days of supplementation, serum 25(OH)D levels were significantly increased in the group who received 10,000IU/day (p < 0.0001) (n = 44) in comparison with the 2,000IU/day group (n = 41), especially in overweight and obese participants, and the higher dose was well tolerated. A fraction of the individuals in our cohort (10/85) developed acute respiratory distress syndrome (ARDS). The median length of hospital stay in these patients with ARDS was significantly different in the participants assigned to the 10,000IU/day group (n = 4; 7 days; IQR: 4–13) and the 2,000IU/day group (n = 6; 27 days; IQR: 12–45) (p = 0.04). Moreover, the inspired oxygen fraction was reduced 7.6-fold in the high dose group (p = 0.049). In terms of blood parameters, we did not identify overall significant improvements, although the platelet count showed a modest but significant difference in those patients who were supplemented with the higher dose (p = 0.0492). In conclusion, the administration of 10,000IU/day of vitamin D3 for 14 days in association with the standard clinical care during hospitalization for COVID-19 was safe, tolerable, and beneficial, thereby helping to improve the prognosis during the recovery process.
... Vitamin D 3 has a variety of pleiotropic functions in many extra-skeletal targets [2]. For instance, it regulates DNA stability, cell proliferation and differentiation, and innate and adaptive immunity [2,[6][7][8]. Increased intestinal absorption of ingested calcium is vitamin D 3 s key function in maintaining calcium homeostasis [4]. Regarding the absorption sites involved, the distal intestine, in addition to the duodenum, which only absorbs 8-10% calcium, plays an important role in intestinal calcium absorption [9][10][11][12]. ...
Article
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Vitamin D3 (D3) is produced endogenously from 7-dehydrocholesterol by irradiation and is an important secosteroid for the absorption of calcium and phosphate. Lithocholic acid (LCA) increases intestinal paracellular calcium absorption in a vitamin D receptor-dependent manner in vitamin D-deficient rats. The plateau zokor (Myospalax baileyi), a strictly subterranean species, and plateau pika are endemic to the Qinghai-Tibet Plateau. To verify whether the zokors were deficient in D3 and reveal the effects of hypoxia on D3 metabolism in the zokors and pikas, we measured the levels of 25(OH)D3, calcium, and LCA, and quantified the expression levels of D3 metabolism-related genes. The results showed an undetectable serum level of 25(OH)D3 and a significantly higher concentration of LCA in the serum of plateau zokor, but its calcium concentration was within the normal range compared with that of plateau pika and Sprague-Dawley rats. With increasing altitude, the serum 25(OH)D3 levels in plateau pika decreased significantly, and the mRNA and protein levels of CYP2R1 (in the liver) and CYP27B1 (in the kidney) in plateau pika decreased significantly. Our results indicate that plateau zokors were deficient in D3 and abundant in LCA, which might be a substitution of D3 in the zokor. Furthermore, hypoxia suppresses the metabolism of D3 by down-regulating the expression of CYP2R1 and CYP27B1 in plateau pika.
... During the critical period (from the child's conception to 2 years of age), vitamin D deficiency can increase the risk of growth retardation [13]. Vitamin D levels affect and have a significant relationship with linear growth and are important for normal growth in children [14][15][16]. On the other hand, vitamin D deficiency is correlated with decreased linear growth and stunting [17]. ...
Article
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Stunting, which results from chronic malnutrition, is common in children from low- and middle-income countries. Several studies have reported an association between obesity and asthma. However, only a handful of studies have identified stunting as a significant risk factor for wheezing, a symptom of asthma, although the underlying mechanism remains unclear. This article aimed to review possible mechanisms underlying asthma in stunted children. Overall, changes in diet or nutritional status and deficiencies in certain nutrients, such as vitamin D, can increase the risk of developing asthma. Vitamin D deficiency can cause linear growth disorders such as stunting in children, with lower levels of 25(OH)D found in underweight and stunted children. Stunted children show a decreased lean body mass, which affects lung growth and function. Low leptin levels during undernutrition cause a Th1–Th2 imbalance toward Th2, resulting in increased interleukin (IL)-4 cytokine production and total immunoglobulin E (IgE). Studies in stunted underweight children have also found an increase in the proportion of the total number of B cells with low-affinity IgE receptors (CD23+). CD23+ plays an important role in allergen presentation that is facilitated by IgE to T cells and strongly activates allergen-specific T cells and the secretion of Th2-driving cytokines. Stunted children present with low vitamin D and leptin levels, impaired lung growth, decreased lung function, and increased IL-4 and CD23+ levels. All of these factors may be considered consequential in asthma in stunted children.
... Vitamin D plays a notable function in managing both the innate and adap-tive immune systems [40]. Studies have demonstrated that 1,25(OH)2D3 is influential on the adaptive immune system, as VDR is expressed in almost all cell types, such as T-cells, Bcells, macrophages, monocytes, and dendritic cells (antigenpresenting cells) [41]. Deficient vitamin D levels are eventually observed in most acquired immune-mediated diseases. ...
Article
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Vitamin D has received considerable optimistic attention as a potentially important factor in many pathological states over the past few decades. However, the proportion of the active form of vitamin D metabolites responsible for biological activity is highly questionable in disease states due to flexible alterations in the enzymes responsible for their metabolism. For instance, CYP3A4 plays a crucial role in the biotransformation of vitamin D and other drug substances. Food-drug and/or drug-drug interactions, the disease state, genetic polymorphism, age, sex, diet, and environmental factors all influence CYP3A4 activity. Genetic polymorphisms in CYP450-encoding genes have received considerable attention in the past few decades due to their extensive impact on the pharmacokinetic and dynamic properties of drugs and endogenous substances. In this review, we focused on CYP3A4 polymorphisms and their interplay with vitamin D metabolism and summarized the role of vitamin D in calcium homeostasis, bone diseases, diabetes, cancer, other diseases, and drug substances. We also reviewed clinical observations pertaining to CYP3A4 polymorphisms among the aforementioned disease conditions. In addition, we highlighted the future perspectives of studying the pharmacogenetics of CYP3A4, which may have potential clinical significance for developing novel diagnostic genetic markers that will ascertain disease risk and progression.
... Vitamin D can inhibit the differentiation of Th1 cells, and the production of inflammatory cytokines such as TNF-α, INF-γ. It could also suppress inflammatory Th1, but induce anti-inflammatory Th2 which produced antiinflammatory cytokines such as IL-4 and IL-5 [66] . Furthermore, the Th17 cells with their production of IL-17A could also be inhibited by Vitamin D at the transcriptional level [67] . ...
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The objective of the surrent study was to summarize the up-to-date studies to investigate the relationship between vitamin D and Hashimoto thyroiditis (HT). An online search of English and Chinese databases was performed. The studies concerned the investigation of the relationship between vitamin D and HT including meta-analysis, meanwhile the heterogeneities were revealed by subgroup analysis. Fourty six elated studies containing 15,336 participants (HT: 6,138 versus control: 9,198) were included. HT patients had lower levels of 25(OH)D3(standardised mean difference, −1.09; 95%CI: [−1.42, −0.75]; P< 0.01), and were more likely to be deficient in 25(OH)D3 (OR, 2.77; 95%CI, [1.88, 3.91]; P < 0.05). Obvious heterogeneities in the results of meta-analysis were down to the difference of detection methods and criteria of vitamin D insufficiency among studies. Vitamin D deficiency was colncluded to have a significant relation with HT.
... Though higher levels of VitD in women with suppressed TSH levels might presumably be due to an increased absorption of VitD in hyperthyroid state, the concept has not been studied. Vitamin D has potent immunomodulatory effects and plays an important role in the pathogenesis of autoimmune diseases [16]. In the classical endocrine pathway, vitamin D enters the circulation attached to a D-binding protein, is first hydroxylated in the liver to 25-hydroxy vitamin D (25(OH) D) and then in the kidney to form the active metabolite, 1, 25 dihydroxy vitamin D (1, 25-(OH)2 D) or calcitriol [17]. ...
Article
Introduction: Vitamin D (VitD) insufficiency is present in over half of population worldwide. Over a billion people worldwide are vitamin D deficient or insufficient. It has been long known that VitD insufficiency contributes to development of osteopenia and osteoporosis. Objective: To assess the serum vitamin D and TSH status in postmenopausal women who have undergone routine blood investigations. Methods: We performed a retrospective review of data of 61 patients in postmenopausal age group (45-75yrs) during their routine blood investigation for the first time at Dept. of Obstetrics and Gynaecology, Shaheed Tajuddin Ahmad Medical College Hospital, Gazipur, Bangladesh from January to March 2021. The data was collected from medical record section and appropriate statistical analysis was done using percentage and frequency. Results: Out of 61 patients Vitamin D was insufficient (10-30 ng/mL) in 34.4% and deficient (<10 ng/mL) in 18.0%, and remaining normal. In 4.9%, TSH was low (less than 0.3 mIU/L) and in 18.0% TSH was high (more than 4.5 mIU/L), while the remaining 77.0 had normal TSH levels (0.3-4.5 mIU/L). 54.5%(n-11) patients with high TSH, had vitamin D deficiency and 18% patients with high TSH had insufficient vitamin D. 100% (n-3) of patients with low TSH had normal vitamin D. 22 patients had normal TSH and normal vitamin D. Conclusion: Prospective longitudinal studies with larger subject numbers and more comprehensive measurement of thyroid function along with examining the indicators of innate immunity may shed light into the underlying pathophysiology and mechanisms involved in the interaction between thyroid function and VitD metabolism. High TSH levels was associated with low vitamin D levels, low TSH levels was associated with normal serum vitamin D level. Hence association was linear between TSH and vitamin D in post-menopausal women.
Article
Background: The urban lifestyle and environment pose a constant immune challenge to city dwellers. A major such challenge is influenza, which creates substantial public health and socio-economic burdens. The global healthcare paradigm has begun emphasizing the importance and cost-effectiveness of self-care in partnership with healthcare professionals such as community pharmacists for the management of mild ailments. For the general public, micronutrient supplementation is an affordable and potentially feasible self-care strategy for immunity enhancement and disease management. At the same time, micronutrient deficiencies are a serious public health concern in both developing and developed areas. Objective: This review focuses on the clinical evidence for the efficacy and safety of three key micronutrients — vitamins C, D and zinc — on respiratory infections. Key findings: These micronutrients are important for optimal immune function through their complementary roles in supporting both innate and adaptive immunity, as well as epithelial barriers. The need to improve public awareness of self-care in prevention and health management is highlighted by recent public health issues and the global fight against antimicrobial resistance. Community pharmacists could play a crucial role in empowering patient autonomy. Conclusion: With this review we aim to offer insights into the supplementation of these micronutrients as a self-care approach to the management of immune health.
Article
Resumen El sistema endocrino de la vitamina D es esencial para mantener la homeostasis del calcio y el fósforo y para prevenir el raquitismo y la osteomalacia. La mayor parte de la vitamina D circulante procede de la síntesis cutánea, por acción de la radiación ultravioleta en el 7-dehidrocolesterol. Solo un 10–20% de la requerida procede de la dieta. Tras una primera hidroxilación hepática, la vitamina D sintetizada en la piel o provista por la dieta se transforma en 25-hidroxivitamina D, compuesto de vida media larga que se utiliza en la clínica como estimador de los depósitos corporales de esta vitamina. Posteriormente, una segunda hidroxilación en el túbulo renal lo transforma en un compuesto activo, el 1,25-dihidroxivitamina D, que se une al receptor intracelular de vitamina D y es capaz de regular la expresión de un gran número de genes. Desde hace años se conocen múltiples efectos extraesqueléticos de la vitamina D, como son la regulación de la función muscular, el crecimiento celular, el sistema inmunitario y la defensa contra las infecciones. Estudios clínicos han relacionado los trastornos de la vitamina D con la aparición de diabetes mellitus, cáncer, enfermedades autoinmunitarias, trastornos metabólicos y enfermedad cardiovascular. La deficiencia de vitamina D es un serio problema de salud pública, dado que su prevalencia alcanza proporciones pandémicas. Por ello, diversas sociedades científicas han definido criterios de insuficiencia y deficiencia de esta vitamina y han emitido recomendaciones para prevenir y tratar esta deficiencia y sus consecuencias clínicas.
Article
Orodispersible film (ODF) is a new dosage form that disperses rapidly in the mouth without water or swallowing. The main ingredient of an ODF is a polymer that can be both of natural or synthetic origin. Maltodextrin is a natural polymer, mainly used in pharmaceutical and nutraceutical fields. This review aims to examine the literature regarding ODFs based on maltodextrin as the platform for developing new products for therapeutical application. ODFs based on maltodextrin contain plasticizers that enhance their flexibility and reduce their brittleness. Surfactants; fillers, such as homopolymer and copolymer of vinylacetate; flavour and sweetener were introduced to improve ODF characteristics. Both water-soluble and insoluble APIs were introduced up to 100 mg per dosage unit. The solvent casting method and hot-melt extrusion are the most useful techniques for preparing ODFs. In particular, the solvent casting method allows manufacturing processes to be developed from a lab scale to an industrial scale. ODFs based on maltodextrin are characterized in terms of mechanical properties, dissolution rate, taste and stability. ODFs made of maltodextrin, developed by IBSA, were tested in vivo to evaluate their bioequivalence and efficacy and were demonstrated to be a valid alternative to the marketed oral dosage forms.
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Mibyou has been defined in traditional oriental medicine as a certain physiological condition whereby an individual is not ill but not healthy; it is also often referred to as a sub-healthy condition. In a society focused on longevity, “Mibyou-care” becomes of primary importance for healthy lifespan expenditure. Functional foods can play crucial roles in Mibyou-care; thus, the search for novel resources of functional food is an important and attractive research field. Mushrooms are the target of such studies because of their wide variety of biological functions, such as immune modulation and anti-obesity and anticancer activities, in addition to their nutritional importance. Basidiomycetes-X (BDM-X; Shirayukidake in Japanese) is a mushroom which has several attractive beneficial health functions. A metabolome analysis revealed more than 470 components of both nutritional and functional interest in BDM-X. Further isolation and purification studies on its components using radical scavenging activity and UV absorbance identified ergosterol, (10E,12Z)-octadeca-10,12-dienoic acid (CLA), 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one (DDMP), formyl pyrrole analogues (FPA), including 4-[2-foemyl-5-(hydroxymethyl)-1H-pyrrole-1-yl] butanamide (FPAII), adenosine and uridine as major components. Biological activities attributed to these components were related to the observed biological functions of BDM-X, which suggest that this novel mushroom is a useful resource for Mibyou-care functional foods and medicines.
Article
Objective Multiple factors being overweight, asthmatic, or being of Asian or black ethnic origins have been reported vis-à-vis the “multisystem inflammatory syndrome in children” (MIS-C). There is an association between these conditions and vitamin D deficiency, which explains why MIS-C is more common in these patients. In the present study, we attempted to retrospective evaluate the 25-hydroxy vitamin D levels of patients with MIS-C, its association with acute phase reactants, its treatment, and clinical status. Methods Patients aged between 1.5 months to 18 years with MIS-C were included in the study. All of the laboratory parameters, treatment, and response to the treatment were evaluated retrospectively. Two groups were formed. Patients had 25‐hydroxycholecalciferol D vitamin < 20 ng/mL in group 1 and ≥ 20 ng/mL in group 2. Results A total of 52 patients were included in the study. There was no statistical difference between groups in terms of acceptance of the intensive care unit treatment (p = 0.29) and response to the first-line treatment (p = 0.56). A lower median lymphocyte count (p = 0.01) and a higher median C-reactive protein (p = 0.04) and procalcitonin (p = 0.01) with N-terminal pro-B-type natriuretic peptide (p = 0.025) values were found in group 1. Conclusion Vitamin D deficiency was associated with an increased inflammatory response in children with MIS-C. More studies are required to determine the potential impact of vitamin D deficiency on the clinical outcome of MIS-C.
Article
Objective Previous studies have shown that vitamin D has regulatory functions in both innate and adaptive immune responses, indicating that it can perform essential roles in host resistance to pathogen infections. This study aimed to verify its effects on Klebsiella pneumoniae (Kp) infection and explore the underlying mechanisms. Methods THP-1-derived macrophages were infected with Kp and then incubated with 1,25(OH)2D3. Autophagy induced by 1,25(OH)2D3 was investigated by western blotting and immunofluorescence. Real-time PCR (qPCR) was performed to determine the expression of inflammatory mediators. Baf A1 and 3-MA were used to inhibit autophagy. The intracellular killing of Kp was measured using qPCR and colony-forming unit assays. RNA interference assays were used to silence VDR or ATG16L1. The lungs of C57BL/6 mice were infected with Kp via intratracheal instillation, and the established pneumonia models were used for in vivo validation experiments. Results Treatment with 1,25(OH)2D3 enhanced the bactericidal activity of macrophages and concomitantly reduced the expression of the pro-inflammatory mediators TNF-α and IL-6. Kp infection led to a lower expression level of VDR in macrophages than in the control, whereas co-treatment with 1,25(OH)2D3 up-regulated VDR expression and robustly induced autophagy via the VDR signaling pathway. Silencing ATG16L1 significantly counteracted autophagy induced by 1,25(OH)2D3 in Kp-infected macrophages. Furthermore, we found that when autophagy activity was diminished by ATG16L1 siRNA or blocked by Baf A1, the ability of 1,25(OH)2D3 to promote macrophages to eliminate Kp infection was obviously impaired, as were its anti-inflammatory effects. These protective efficacies of 1,25(OH)2D3 against Kp infection were also validated in vivo using a mouse model of pneumonia. Conclusions The present study demonstrated the protective features of 1,25(OH)2D3 in macrophages against Kp infection and may provide evidence for further exploration of its potential as an adjunctive therapy agent for the treatment of bacterial infections.
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Background and Aim. Low serum levels of 25-hydroxyvitamin D3 are associated with an increased risk of Acute Respiratory Infection (ARI) that is among the most important causes of morbidity and mortality in children under 5 years old. We describe the clinical behavior of acute respiratory infections in patients under five years ago in one sanitary institution in Colombia after VD3 supplementation. Material and Methods. A case series was conducted on 38 patients of both genders aged less to 5 years ago was included. Participants were supplied 50,000 units of VD3 orally each month for three months. The number of events, consultations for emergency services, and hospitalization due to acute respiratory infections (ARIs) before and after VD3 administration were described. Results. The average age of the participants was 25.81 ± 17.50 months. The average clinical ARIs per month was 4.02 (95% CI 3.64-4.40) before VD3 administration. Fewer episodes at the end of the three cycles was found at 2.23/month (95% CI 1.81-2.65; p=0.0230). The average consultations for emergency services during the three months before VD3 administration was 2.15 (95% CI 1.77-2.53). After three months of treatment, the average use of emergency services decreased to 0.52 (95% CI 0.37-0.72; p=0.0180). After the administration of the three doses of VD3, only one patient required hospitalization (2.63%; : 0.026 (IC95% 0.02-0.03; p=0.0368)). Conclusions. The administration of vitamin D3 could have a benefit in decreasing the number of episodes, emergencies, and hospitalization for ARI in children under five years old. Trial studies are required to determine this potential benefit.
Article
Purpose To investigate a causal relationship between Vitamin D levels and non-infectious uveitis and scleritis using Mendelian randomization (MR) techniques. Design Two-sample Mendelian randomization case-control study. Methods Setting: Biobank of an academic, integrated health care system. Patient Population: 375 cases with a non-infectious uveitis and/or scleritis diagnosis and no diagnosis of infectious, trauma-related, or drug-induced uveitis/scleritis. 4,167 controls with no uveitis or scleritis diagnosis. Main Outcome and Measures: Causal effect estimates of low 25-hydroxy Vitamin D (25OHD) on uveitis/scleritis risk. Results We found an association of genetically decreased 25OHD with uveitis/scleritis risk [odds ratio (OR) = 2.16, 95% confidence interval (CI) = 1.01 – 4.64, P = 0.049, per standard deviation (SD) decrease of log25OHD]. In a first sensitivity MR analysis excluding the genetic variants that are unlikely to have a role on biologically active 25OHD, effect estimates were consistent with those from the primary analysis (OR = 2.38, 95% CI =1.06 – 5.36, P = 0.035, per SD of log25OHD). Furthermore, in a second sensitivity analysis using only the six variants within the CYP2R1 locus (which encodes 25OHD hydroxylase, the liver enzyme responsible for converting Vitamin D to 25OHD), genetically decreased 25OHD was strongly associated with increased uveitis/scleritis risk (OR = 6.42, 95% CI = 3.19 -12.89, P = 1.7 × 10⁻⁷, per SD of log25OHD). Conclusions Our findings suggest a causal relationship between low Vitamin D levels and higher risk of non-infectious uveitis and scleritis. Vitamin D supplementation may be a low-cost, low-risk intervention to mitigate non-infectious uveitis and scleritis risk and should be explored in a prospective trial.
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Background Vitamin D has been known to be associated with asthma. However, the association between vitamin D status and asthma, lung function as well as hospitalization among adults remains unclear. Objective To investigate the role of serum vitamin D in asthma prevalence, lung function, and asthma control in adults. Methods Multivariable logistic regression was applied to assess the relationship between serum vitamin D and asthma prevalence, lung function (FEV1, FVC, and FEV1/FVC), current wheeze, and asthma-linked hospitalizations in a cross-sectional study of 435,040 adults aged 37–73 years old from the UK Biobank. Results Compared to vitamin D deficiency, the odds of asthma were decreased by 6.4% [adjusted odds ratio ( aOR ) = 0.936; 95% CI : 0.911–0.962; p < 0.001] and 9.8% ( aOR = 0. 0.902; 95% CI : 0.877–0. 0.927; p < 0.001) in individuals with insufficient and optimal vitamin D concentration, respectively, in the fully adjusted model. In total asthmatic patients, serum vitamin D was obviously and positively related with FEV1 (β = 1.328 ml, 95% CI = 0.575–2.080), FVC (β = 2.018 ml, 95% CI = 1.127–2.908), and FEV1/FVC (β = 0.006%, 95% CI = 0.002–0.010). Asthmatic patients whose vitamin D level was in the deficient category had 9.3–19.9% higher odds of current wheeze than insufficient categories ( aOR = 0.907; 95% CI : 0.861–0.957; p < 0.001) and optimal categories ( aOR = 0.801; 95% CI : 0.759–0.845; p < 0.001), but the relationship between vitamin D and asthma hospitalization was not significant. Conclusion Vitamin D deficiency was related to higher odds of asthma and current wheeze, and lower lung function in a large sample size study of British adults. Our results indicate a potential positive impact of serum vitamin D on asthma occurrence and disease control in adults.
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A randomized complete block design experiment was conducted to determine the safety and efficacy of supplementation of increasing concentrations of a novel, bacterial fermentation-derived vitamin D source on growth performance and tissue deposition of 25-hydroxycholecalciferol (25OHD3) in growing swine. Dietary treatments were as follows: commercial control with vitamin D3 (CON) at NRC recommended concentrations and 3 diets composed of CON + increasing inclusions (25, 50, and 250 µg/kg equivalent) of 25OHD3 from a novel source (CON+25; CON+50; and CON+250 respectively). Pigs (n = 144) were assigned to 24 pens which were allotted to 1 of the 4 dietary treatments and fed for 42 d. Blood samples were collected for 25OHD3 concentration determination and individual body weights were measured on experimental d 0, 39, and 63. On d 42, tissues from 48 pigs (12 pigs per dietary treatment) were analyzed for 25OHD3 concentration. No differences were observed in growth performance. Day 39 serum 25OHD3 concentrations were greatest in CON+250-fed pigs and linearly decreased as dietary 25OHD3 inclusion decreased (P < 0.0001). On d 42, tissue 25OHD3 concentrations increased linearly as 25OHD3 increased in the diet (P < 0.0001). On d 63, 21 d after dietary 25OHD3 withdrawal, serum 25OHD3 concentrations of all 25OHD3-fed pigs decreased to that of or within 2.76 ± 0.89 ng/mL of CON-fed pigs which demonstrates that feeding 250 µg/kg 25OHD3 is well tolerated by growing pigs and will clear the body within 21 d.
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The publication of our recent randomized controlled trial (RCT) showing that vitamin D could protect the β-cells during the honeymoon phase of type 1 diabetes (T1D) has led to calls for guidance for vitamin D supplementation during the critical phase of type 1 diabetes. Prolonging the partial clinical remission (PR) phase of TID improves glycemic control and reduces long-term complications of T1D. This RCT randomized 36 children and adolescents to either receive vitamin D 2 (ergocalciferol, given as 50,000 international units per week for 2 months and then every other week for 10 months) or a placebo. The results showed that vitamin D significantly decreased the temporal rise in both hemoglobin A1c at a mean rate of changes of 0.14% every 3 months versus 0.46% every 3 months for the placebo group (p=0.044); and in the functional marker of PR, the insulin-dose adjusted A1c at a mean rate of change of 0.30% every 3 months versus 0.77% every 3 months for the placebo group, (p=0.015). We recommend a baseline estimation of 25(OH)D concentration at the time of diagnosis of T1D, and to begin vitamin D supplementation if serum 25(OH)D concentration is <30 ng/mL, to maintain serum 25(OH)D concentrations between 30-60 ng/mL. If serum 25(OH)D concentration is >30 ng/mL, monitor vitamin D status with serial 25(OH)D estimations; and initiate vitamin D supplementation if serum 25(OH)D concentrations drop to <30 ng/mL. Continue vitamin D supplementation for at least one year to ensure optimal benefit from vitamin D supplementation during the partial clinical remission phase of type 1 diabetes.
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ÖZ: Amaç: Bu çalışmada, evre 3-5 Kronik böbrek hastalarında (KBH) vitamin D replasmanının CD3+, CD4+, CD8+ ve CD14+ hematopoietik hücre alt gruplarındaki vitamin D reseptör (VDR) yüzdesi ile inflamatuar belirteçlerle ilişkisini değerlendirmeyi amaçladık. Yöntem: Bu prospektif çalışmada evre 3-5 KBH’sı olan; tahmini glomerüler filtrasyon hızı (tGFH) ≤60ml/dk/1,73m2 olan 81 hasta katıldı. Serum kreatinin, tGFH, intakt parathormon (iPTH), 25 OH vitamin D düzeyleri, CRP, nötrofil, lenfosit değerleri ve CD3+, CD4+, CD8+, CD14+ hematopoietik hücrelerde VDR yüzdeleri hesaplandı. Hastalar, 25 OH VD3 düzeylerine göre Vitamin D eksikliği tanısıyla (<20 ve ≥20 ng/dl) iki gruba, KBH evrelerine göre (evre 3-5) üç gruba, D vitamini kullanımı durumuna göre (kullanmıyor, kalsitriol veya 25 OH vitamin D) üç gruba ayrıldı. Bulgular: Vitamin D eksikliği tanısıyla iki gruba ayrılan hastalarda aktif D vitamini kullanımı, kreatinin, tGFH ve iPTH düzeyleri arasında istatistiksel anlamda fark tespit edildi (p:0,04, p:0,008, p:0,02 ve p:0,002). CRP ve nötrofil /lenfosit oranı arasında istatistiksel fark tespit edilmedi (p:0,95, p:0,63). Hastaları KBH evrelerine göre gruplandırdığımızda iPTH düzeylerinde istatistiksel fark tespit edildi (p:0,001). Hastaları D vitamini kullanımı durumuna göre üç gruba ayırdığımızda kreatinin, tGFH, iPTH ve 25 OH vitamin D3 düzeyleri arasında istatistiksel fark tespit edildi (p:0,00, p:0,00, p: 0,02 ve p:0,006). CD3 +, CD4 +, CD8 +, CD14 + hematopoietik hücrelerde VDR yüzdeleri arasında bir fark tespit edilmedi (p:0,17, p:0,15, p:0,14, p:0,31). Lenfosit düzeyleriyle tGFH değerleri arasında istatistiksel bir korelasyon vardı (r:0,28, p:0,011). Lenfosit düzeyleriyle CD8+ hücrelerin VDR yüzdesi değerleri arasında istatistiksel bir korelasyon vardı (r:0,224, p:0,046). Sonuç: Replasman tedavileri ile VDR yüzdelerinin tüm evrelerde benzer oranlarda tutulabileceği, inflamasyonda azalma sağlanmış olabileceğinden kaynaklı olabilir. ANAHTAR KELİMELER: İnflamasyon, Kronik Böbrek Hastalığı, Vitamin D, Vitamin D Reseptör Düzeyi
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Systemic lupus erythematosus (SLE) is a highly heterogeneous autoimmune disease that primarily affects women. Currently, in the search for the mechanisms of SLE pathogenesis, the association of lifestyle factors such as diet, cigarette smoking, ultraviolet radiation exposure, alcohol and caffeine-rich beverage consumption with SLE susceptibility has been systematically investigated. The cellular and molecular mechanisms mediating lifestyle effects on SLE occurrence, including interactions between genetic risk loci and environment, epigenetic changes, immune dysfunction, hyper-inflammatory response, and cytotoxicity, have been proposed. In the present review of the reports published in reputable peer-reviewed journals and government websites, we consider the current knowledge about the relationships between lifestyle factors and SLE incidence and outline directions of future research in this area. Formulation of practical measures with regard to the lifestyle in the future will benefit SLE patients and may provide potential therapy strategies.
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The interest in studying synthesis, metabolism and effect of vitamin D has increased recently due to the world tendency to decrease its intake and due to new knowledge about the mechanisms of its active metabolite effects in human organism. According to certain research, deficiency of vitamin D is associated with the increased risk for the development of infectious diseases. As a result of the given study it has been established that patients with liver cirrhosis and with vitamin D deficiency often diagnose bacterial infections, which needs to determine the status of vitamin D and if necessary to correct its content in the patients with liver cirrhosis.
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Vitamin D exerts important extra-skeletal effects, exhibiting an exquisite immune regulatory ability, affecting both innate and adaptive immune responses through the modulation of immunocyte function and signaling. Remarkably, the immune function of working skeletal muscle, which is fully recognized to behave as a secretory organ with immune capacity, is under the tight control of vitamin D as well. Vitamin D status, meaning hormone sufficiency or insufficiency, can push toward strengthening/stabilization or decline of immune surveillance, with important consequences for health. This aspect is particularly relevant when considering the athletic population: while exercising is, nowadays, the recommended approach to maintain health and counteract inflammatory processes, “too much” exercise, often experienced by athletes, can increase inflammation, decrease immune surveillance, and expose them to a higher risk of diseases. When overexercise intersects with hypovitaminosis D, the overall effects on the immune system might converge into immune depression and higher vulnerability to diseases. This paper aims to provide an overview of how vitamin D shapes human immune responses, acting on the immune system and skeletal muscle cells; some aspects of exercise-related immune modifications are addressed, focusing on athletes. The crossroad where vitamin D and exercise meet can profile whole-body immune response and health.
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Background: The recent severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has resulted in millions of confirmed cases of infection and death. Vitamin D modulates the adaptive and innate immune systems; therefore, vitamin D deficiency may be related to the severity of coronavirus disease 2019 (COVID-19). Methods: This study was performed on 122 COVID-19 patients and 122 non-COVID-19 individuals to determine the possible relationship between vitamin D deficiency and COVID-19 severity. Besides, the relationship between vitamin D status and the severity of disease was investigated in 49 patients without an underlying disease. The COVID-19 severity was defined based on O2 saturation, respiratory rate, and pulmonary involvement. Also, vitamin D status was defined as follows: vitamin D deficiency (< 30 ng/mL) and vitamin D sufficiency (≥ 30 ng/mL). Results: The mean age of 122 COVID-19 patients, including 71 (58.2%) male patients and 51 (41.8%) women patients, was 59 ± 16 years in this study, while the mean age of the controls, including 61 male participants and 61 female participants, was 48 ± 13 years (P < 0.05). The mean vitamin D level was 34.14 ± 1 ng/mL in the patients and 32.94 ± 1 ng/mL in the controls (P = 0.872). However, there was no significant correlation in none of all the 122 patients and 49 patients without an underlying disease (P = 0.074, P = 0.261). Conclusions: Based on the present findings, the correlation between vitamin D status and COVID-19 severity was not significant neither in 122 patients, and nor in 49 patients without an underlying disease.
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SummaryThis review describes the vitamin D status in different regions of the world with the objective of understanding the scope of hypovitaminosis D and the factors related to its prevalence that may contribute to the pathogenesis of osteoporosis and fragility fractures. IntroductionVitamin D status has been linked to the pathogenesis of hip fractures as well as other skeletal and non-skeletal disorders. The purpose of this review is to provide a global perspective of vitamin D status across different regions of the world and to identify the common and significant determinants of hypovitaminosis D. MethodsSix regions of the world were reviewed—Asia, Europe, Middle East and Africa, Latin America, North America, and Oceania—through a survey of published literature. ResultsThe definition of vitamin D insufficiency and deficiency, as well as assay methodology for 25-hydroxyvitamin D or 25(OH)D, vary between studies. However, serum 25(OH)D levels below 75nmol/L are prevalent in every region studied whilst levels below 25nmol/L are most common in regions such as South Asia and the Middle East. Older age, female sex, higher latitude, winter season, darker skin pigmentation, less sunlight exposure, dietary habits, and absence of vitamin D fortification are the main factors that are significantly associated with lower 25(OH)D levels. ConclusionReports from across the world indicate that hypovitaminosis D is widespread and is re-emerging as a major health problem globally.
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An inadequate serum vitamin D status is commonly seen in elderly people as the result of various risk factors interacting in this population. Apart from the well-known effects on bone metabolism, this condition is also associated with muscle weakness, predominantly of the proximal muscle groups. Muscle weakness below a certain threshold affects functional ability and mobility, which puts an elderly person at increased risk of falling and fractures. Therefore, we wanted to determine the rationale behind vitamin D supplementation in elderly people to preserve and possibly improve muscle strength and subsequently functional ability. From experimental studies it was found that vitamin D metabolites directly influence muscle cell maturation and functioning through a vitamin D receptor. Vitamin D supplementation in vitamin D-deficient, elderly people improved muscle strength, walking distance, and functional ability and resulted in a reduction in falls and nonvertebral fractures. In healthy elderly people, muscle strength declined with age and was not prevented by vitamin D supplementation. In contrast, severe comorbidity might affect muscle strength in such a way that restoration of a good vitamin D status has a limited effect on functional ability. Additional research is needed to further clarify to what extent vitamin D supplementation can preserve muscle strength and prevent falls and fractures in elderly people.
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Background: Although Vitamin D is best known as a calcium homeostasis modulator, it also has immune modulating potential, as shown by its protective effect against MS development, supported by reduced disease risk associated with sun exposure and Vitamin D supplement use. Elevated Vitamin D blood levels have also been associated with lower risk of MS. Objective: To study the immunomodulatory effects of Vitamin D in MS. Methods: Serum 25(OH)D3 and 1,25(OH)2D3 levels were measured using ELISA in 58 relapsing remitting MS (RRMS) patients during remission, 34 RRMS patients during relapses, 40 primary progressive MS (PPMS) subjects and 60 healthy controls. Cell proliferation was measured using [3H]-thymidine incorporation assays. Vitamin D receptor (VDR), α1-hydroxylase, and indoleamine 2,3-dioxygenase (IDO) expression was measured by RT-PCR, while cytokine production was evaluated using ELISPOT. CD4+CD25+ regulatory T cells were studied using flow cytometry. Results: 25(OH)D3 and 1,25(OH) 2D3 levels were significantly lower in RRMS patients than in controls, more during relapses than remissions. By contrast, PPMS patients showed similar levels to controls. Proliferation of both freshly isolated CD4+ T cells and MBP-specific T cells was inhibited by 1,25(OH)2D 3. Activated Vitamin D also enhanced IL-10 producing cell development, and reduced IL-6, and IL-17 secreting cell numbers. 1,25(OH) 2D3 induced VDR expression in both activated and resting cells. Interestingly, T cells metabolized 25(OH)D3 into biologically active 1,25(OH)2D3, since they constitutively express α1-hydroxylase. Finally, 1,25(OH)2D3 also increased expression and biological activity of IDO, triggering significant increase in the number of CD4+CD25+ regulatory T cells. Conclusions: 1,25(OH) 2D3 plays an important role in T cell homeostasis during RRMS. Correction of its deficiency may prove useful in the treatment of the disease.
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The expression of inducible nitric oxide synthase (iNOS) expression and release of nitric oxide (NO) from macrophages are markedly increased in granulomatous infections. Activation of macrophages 1α-hydroxylase results in an increase of 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3]. However, the significance of this increased production is not completely understood. In this study, we analyzed 1,25(OH)2D3 and NO production in patients with tuberculosis infection and hypercalcemia and used lipopolysaccharide (LPS) to stimulate RAW 264.7 cells in an attempt to assess iNOS expression and gaseous NO production regulated by 1,25(OH)2D3. Peroxynitrite (OONO−) production and lactate dehydrogenase activity were also examined. Without additional stimulation, peripheral-blood mononuclear cells (PBMCs) from patients with tuberculosis converted more 25-hydroxyvitamin D3 to 1,25(OH)2D3 than did those from normal controls. These PBMCs released less NO than did those from control subjects, at baseline and in the stimulated state. We found that 1,25(OH)2D3 dose-dependently inhibited iNOS messenger RNA expression of the LPS-stimulated RAW 264.7 cells and also significantly reduced the gaseous NO release and OONO− production. Paralleling the 1,25(OH)2D3-induced inhibition of NO release were reductions in OONO− and LDH production. In conclusion, 1,25(OH)2D3 inhibited iNOS expression and reduced NO production by LPS-stimulated macrophages in the range of physiological doses. Inhibition of the NO surge was coupled with a reduction in OONO− and LDH production. Increased 1,25(OH)2D3 production and decreased release of NO from the PBMCs of patients with tuberculosis and hypercalcemia were also noted. We propose that 1,25(OH)2D3 production by macrophages may protect themselves against oxidative injuries caused by the NO burst. In the case of tuberculosis infection, increased 1,25(OH)2D3 synthesis may further contribute to the development of an unwanted phenomenon—hypercalcemia.
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Summary 1,25 dihydroxyvitamin D3, the active form of vitamin D, has immunomodulatory properties in vitro and in vivo. We report that treatment with 1,25 dihydroxyvitamin D3 (5 g/kg on alternate days) prevents the development of clinical diabetes in NOD mice, an animal model of human autoimmune diabetes. Diabetes incidence in female NOD mice at the age of 200 days was reduced to 8% in the 1,25 dihydroxyvitamin D treated group vs 56% in the control group (p3 resulted in a complete normalisation of the capacity to induce suppressor mechanisms in an autologous MLR, which is severely depressed in control NOD mice. The existence of such suppressor cells was confirmed in transfer experiments, whereby cotransfer of splenocytes from 1,25 dihydroxyvitamin D3 treated NOD mice prevented diabetes transfer by splenocytes from diabetic NOD mice into irradiated, 6–8-week-old male NOD mice. Other known immune defects of the NOD mice, such as defective natural killer cell killing of YAC-1 targets and defective thymocyte activation by anti-CD3 were not corrected. The pharmacological doses of 1,25 dihydroxyvitamin D3 were universally well tolerated as reflected by a normal weight gain of the mice. Serum calcium was increased (2.5±0.2 vs 2.2±0.2 mmol/l in the control group, P3 can prevent diabetes in NOD mice, probably through the correction of their defective suppressor function.
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Background. Type 1 diabetes is characterized by the presence of an autoimmune memory, responsible for the destruction of even syngeneic islet grafts. This recurrence of autoimmunity is partly responsible for the need of extensive immunosuppression in pancreas and islet transplantation in type 1 diabetic patients. The aim of the study was to evaluate the capacity of a 20-epi-analog of vitamin D3, KH1060, both alone and in combination with cyclosporine (CsA) to prevent diabetes recurrence in syngeneic islet grafts in nonobese diabetic (NOD) mice. Methods. Spontaneously diabetic NOD mice grafted with syngeneic islets(n=500) under the kidney capsule were treated with KH1060, CsA, or a combination of both drugs from the day before transplantation until recurrence or 60 days after transplantation. Results. Vehicle-treated mice showed a recurrence of diabetes in 100% of cases (n=17) within 4 weeks. Treatment with high doses of CsA (15 mg/kg/day) or KH1060 (1 μg/kg/2 days) significantly prolonged islet survival (60 days and 50 days, respectively, versus 9.5 days in controls;P<0.001 and P<0.0001). Mice treated with subtherapeutical doses of both drugs combined (KH1060 0.5μg/kg/2 days + CsA 7.5 mg/kg/day) had significant prolongation of graft survival (48 days; P<0.001) and more importantly, four of five mice that were still normoglycemic 60 days after transplantation showed no recurrence after discontinuation of all treatment. Histology of the grafts of control and combination-treated mice demonstrated that graft infiltration and islet destruction were less severe in grafts of combination-treated mice. Cytokine mRNA analysis in the grafts 6 days after transplantation revealed a clear suppression of interleukin-12 and T helper 1 cytokines and higher levels of interleukin-4 in combination-treated mice. Conclusions. KH1060, an analog of 1,25(OH)2D3, delays autoimmune disease recurrence after syngeneic islet transplantation in NOD mice, both alone and especially in combination with CsA, possibly restoring tolerance to β cells in 30% of cases.
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Immune cells carry receptors for 1,25-dihydroxyvitamin D3 [1,25(OH)2D3; vitamin D receptor (VDR)] and individuals with severe vitamin D deficiency have immune abnormalities. The aim of this study was to investigate the role of vitamin D in the immune system by studying VDR-knockout (VDR-KO) mice. VDR-KO mice had the same metabolic phenotype as rachitic animals with severe hypocalcemia. Leukocytosis, lymphocyte subset composition in different immune organs, and splenocyte proliferation to several stimuli were normal, except for a lower response to anti-CD3 stimulation (simulation index [SI] of 13 ± 4 vs. 24 ± 9 in wild-type mice; p < 0.01). Macrophage chemotaxis was impaired (41 ± 19% vs. 60 ± 18% in wild-type mice; p < 0.01) but phagocytosis and killing were normal. In vivo rejection of allogeneic (31 ± 12 days vs. 45 ± 26 days of survival in wild-type mice, NS) or xenogeneic (10 ± 2 days vs. 16 ± 9 days of survival in wild-type mice, NS) islet grafts was comparable with wild-type mice. Surprisingly, VDR-KO mice were protected from low-dose streptozotocin-induced diabetes mellitus (LDSDM; 5% vs. 65% in wild-type mice; p < 0.001). Correcting hypocalcemia by use of lactose-rich or polyunsaturated fat-rich diets fully restored the immune abnormalities in vitro and the sensitivity to diabetes in vivo. On the other hand, treatment with 1,25(OH)2D3 protected wild-type mice against diabetes but did not protect normocalcemic VDR-KO mice. We conclude that immune defects observed in VDR-KO mice are an indirect consequence of VDR disruption because they can be restored by calcium homeostasis normalization. This study proves that although 1,25(OH)2D3 is a pharmacologic and probably a physiological immunomodulator, its immune function is redundant. Moreover, we confirm the essential role of calcium in the immune system.
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An inadequate serum vitamin D status is commonly seen in elderly people as the result of various risk factors interacting in this population. Apart from the well-known effects on bone metabolism, this condition is also associated with muscle weakness, predominantly of the proximal muscle groups. Muscle weakness below a certain threshold affects functional ability and mobility, which puts an elderly person at increased risk of falling and fractures. Therefore, we wanted to determine the rationale behind vitamin D supplementation in elderly people to preserve and possibly improve muscle strength and subsequently functional ability. From experimental studies it was found that vitamin D metabolites directly influence muscle cell maturation and functioning through a vitamin D receptor. Vitamin D supplementation in vitamin D-deficient, elderly people improved muscle strength, walking distance, and functional ability and resulted in a reduction in falls and nonvertebral fractures. In healthy elderly people, muscle strength declined with age and was not prevented by vitamin D supplementation. In contrast, severe comorbidity might affect muscle strength in such a way that restoration of a good vitamin D status has a limited effect on functional ability. Additional research is needed to further clarify to what extent vitamin D supplementation can preserve muscle strength and prevent falls and fractures in elderly people.
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The functional status indicator for vitamin D, for both safety and efficacy, is serum 25-hydroxyvitamin D concentration. Efficacy for several health endpoints requires levels of 80 nmol/L or higher. Toxicity occurs at levels of 500 nmol/L or higher. The input needed for efficacy, in addition to typical food and cutaneous inputs, will usually be 1000-2000 IU/day of supplemental cholecalciferol. Toxicity is associated only with excessive supplemental intake (usually well above 20,000 IU/day). (C) 2008 International Life Sciences Institute.
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1,25-dihydroxyvitamin D(3) (calcitriol) regulates immune responses, e.g., inhibits expression of IgE by B cells and enhances expression of IL-10 by dendritic cells and T cells. We report here that activation of human B cells by B cell receptor, CD40 and IL-4 signals induces expression of the gene for 25-hydroxyvitamin-D3-1alpha-hydroxylase (CYP1alpha). Accordingly, these B cells generate and secrete significant amounts of calcitriol. In activated B cells calcitriol induces expression of the genes Cyp24, encoding a vitamin D hydroxylase, and Trpv6, encoding a calcium selective channel protein. Calcitriol enhances IL-10 expression of activated B cells more than threefold, both by recruiting the vitamin D receptor to the promoter of Il-10, and to lesser extent by modulation of calcium-dependent signaling. The molecular link in activated B cells between vitamin D signaling, expression of IgE and IL-10, and their ability to produce calcitriol from its precursor, suggest that pro-vitamin D (25-hydroxyvitamin D(3)) can be used as a modulator of allergic immune responses.
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Besides its actions on minerals and bone, the bioactive vitamin D metabolite, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), has important immunomodulatory properties. Within the immune system, dendritic cells represent key targets for this hormone and 1,25(OH)2D3-induced changes in their phenotype and function ultimately affects T lymphocytes. However, the presence of vitamin D receptors (VDR) in activated T cells proposes additional mechanisms for 1,25(OH)2D3 to directly regulate T cell responses. Here, we investigated the expression and kinetics of vitamin D-related genes in human activated T lymphocytes. Different activation stimuli elicited increased VDR- and 1-alpha-hydroxylase expression, with a highly similar kinetic pattern. Addition of 1,25(OH)2D3 effectively triggered VDR signaling, as evidenced by 24-hydroxylase induction, but only when introduced to T lymphocytes expressing high levels of VDR. This enhanced degree of VDR signaling correlated with a stronger inhibition of cytokines (IFN-gamma, IL-10) and modulation of homing receptor expression (CCR10, CLA) in long-term T cell cultures. Importantly, chronic 1,25(OH)2D3-exposure further amplified VDR signaling and the concomitant T cell modulating effects. In conclusion, we validate T cells as direct targets for 1,25(OH)2D3 and provide this optimized in vitro model to improve our understanding of the role of vitamin D as a direct regulator of T cell responses.
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The vitamin D binding protein (DBP) is a multifunctional, albumin-like plasma protein that often requires cell surface binding to mediate some of its diverse functions. DBP binds to several different molecules on the external face of the plasma membrane indicating that it may possess distinct cell binding sequences. In this report, surface plasmon resonance was utilized to evaluate the relative binding of the human myeloid cell line U937 to immobilized recombinant expressed DBP in order to identify cell localization sequences. U937 cells showed robust binding to immobilized native DBP, but essentially no interaction when sensor chips were coated with beta(2)-microglobulin or BSA. The cell-DBP interaction was completely eliminated if cells were pretreated with soluble DBP. Recombinant DBP domains and truncated domains were next evaluated to determine the location of cell binding regions. Domains I (amino acids 1-191) and III (379-458), but not domain II (192-378), could support cell binding. Further evaluation of domain I, using truncated proteins and overlapping peptides, demonstrated that a single amino acid sequence, residues 150-172 (NYGQAPLSLLVSYTKSYLSMVGS), mediated cell binding. The domain III cell binding region was investigated using truncated versions of domain III fused to full-length domain II that served as a scaffold. These experiments indicated that the cell binding sequence is located in the first portion of that domain (379-402: ELSSFIDKGQELCADYSENTFTEY). Overlapping peptides spanning this sequence could partially block cell binding only when used in combination. We conclude that DBP contains two cell localization sequences that may be required for some of the multiple functions of this protein.
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Vitamin D is a fat-soluble vitamin that plays an important role in bone metabolism and seems to have some anti-inflammatory and immune-modulating properties. In addition, recent epidemiologic studies have observed relationships between low vitamin D levels and multiple disease states. Low vitamin D levels are associated with increased overall and cardiovascular mortality, cancer incidence and mortality, and autoimmune diseases such as multiple sclerosis. Although it is well known that the combination of vitamin D and calcium is necessary to maintain bone density as people age, vitamin D may also be an independent risk factor for falls among the elderly. New recommendations from the American Academy of Pediatrics [corrected] address the need for supplementation in breastfed newborns and many questions are raised regarding the role of maternal supplementation during lactation. Unfortunately, little evidence guides clinicians on when to screen for vitamin D deficiency or effective treatment options.