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Independent and Combined Effects of Particulate Matter and Sleep Deprivation on Human Skin Barrier
Abstract
The exposome encompasses all factors people encounter through life, with the skin constantly exposed. While particulate matter (PM) and sleep deprivation are known to contribute to barrier dysfunction, their combined effects remain unclear.
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Acute sleep deprivation has aroused widespread concern and the relationship between acute sleep deprivation and cortisol levels is inconsistent. This study aimed to explore additional evidence and details. The PubMed, Web of Science, EMBASE, CLINAHL and Cochrane databases were searched for eligible studies published up to June 7, 2023. All analyses were performed using Review Manager 5.4 and Stata/SE 14.0. A total of 24 studies contributed to this meta-analysis. There was no significant difference in cortisol levels between participants with acute sleep deprivation and normal sleep in 21 crossover-designed studies (SMD = 0.18; 95% CI: –0.11, 0.45; p = 0.208) or 3 RCTs (SMD = 0.26; 95% CI: –0.22, 0.73; p = 0.286). Subgroup analysis revealed that the pooled effects were significant for studies using serum as the sample (SMD = 0.46; 95%CI: 0.11, 0.81; p = 0.011). Studies reporting cortisol levels in the morning, in the afternoon and in the evening did not show significant difference (p > 0.05). The pooled effects were statistically significant for studies with multiple measurements (SMD = 0.28; 95%CI: 0.03, 0.53; p = 0.027) but not for studies with single cortisol assessments (p = 0.777). When the serum was used as the test sample, the cortisol levels of individuals after acute sleep deprivation were higher than those with normal sleep.
The diabetes mellitus (DM) skin shows skin barrier dysfunction and skin lipid abnormality, similar to conditions induced by systemic or local glucocorticoid excess and aged skin. Inactive glucocorticoid (GC) is converted into active glucocorticoid by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Hyperglycemia in DM and excessive GC are known to increase endoplasmic reticulum (ER) stress. We hypothesized that hyperglycemia affects systemic GC homeostasis and that the action of skin 11β-HSD1 and GC contributes to increased ER stress and barrier defects in DM. We compared 11β-HSD1, active GC, and ER stress between hyperglycemic and normoglycemic conditions in normal human keratinocytes and db/db mice. 11β-HSD1 and cortisol increased with time in keratinocyte culture under hyperglycemic conditions. 11β-HSD1 siRNA-transfected cells did not induce cortisol elevation in hyperglycemic condition. The production of 11β-HSD1 and cortisol was suppressed in cell culture treated with an ER stress-inhibitor. The 14-week-old db/db mice showed higher stratum corneum (SC) corticosterone, and skin 11β-HSD1 levels than 8-week-old db/db mice. Topical 11β-HSD1 inhibitor application in db/db mice decreased SC corticosterone levels and improved skin barrier function. Hyperglycemia in DM may affect systemic GC homeostasis, activate skin 11β-HSD1, and induce local GC excess, which increases ER stress and adversely affects skin barrier function.
Background:
Although particulate matter likely provokes inflammatory reactions in those with chronic skin disorders like atopic dermatitis, no study has examined the relationship between particulate matter and psoriasis exacerbation.
Objective:
This study evaluated possible associations between particulate matter and hospital visits for psoriasis patients in 7 major cities in South Korea.
Methods:
We investigated the relationship between psoriasis and particulate matter. To do this, we used psoriasis patient data from the Korean National Health Insurance Service database. In addition, PM10 and PM2.5 concentration data spanning a 3-year time frame were obtained from the Korea Environment Corporation.
Results:
A pattern analysis generated by the sample cross-correlation function and time series regression showed a correlation between particulate matter concentration and the number of hospital visits by psoriasis patients. However, the prewhitening method, which minimizes the effects of other variables besides particulate matter, revealed no correlation between the two.
Conclusion:
This study suggests that particulate matter has no impact on hospital visit frequency among psoriasis patients in South Korean urban areas.
Cutaneous homeostasis is modulated by sleep. Although there is little evidence about the efficacy of medications topically applied in the morning compared to those administered in the evening, they are commonly prescribed to be used overnight. Poor sleep may affect the tegument, but its repercussion on dermatological therapy is not clear. This communication aims to carry out an overview on the relationship between sleep and the skin, particularly in respect of the effectiveness of topical substances during the night versus the day; and the possible impact of sleep dysregulation on these treatments. Features related to this external organ, involving hydration, blood flow, and the permeability of the cell barrier have physiological variations in sleep period. Our hypothesis is that sleep loss could alter drug absorption in the dermis and impair the success of the treatment. This can depend on the integrity of the mechanical skin barrier, and the enzymatic process after drug penetration, which may be influenced by the circadian rhythm. We raise the role of sleep disturbance in relation to skin aging and the cutaneous microbiota. The organ integrity and local immunology can be guided by sleep distress, which can modify the control of dermatological diseases. Future comparative analyses are warranted to explore the possible changes of the integumentary system influenced by circadian rhythm, and interference in response to topical dermal treatments. We emphasize the importance of sufficient sleep to improve the clinical management of several dermatosis and cosmetic complaints that need percutaneous therapeutics.
Background:
The influence of airborne particulate matter (PM) on skin has primarily been studied in patients with skin diseases such as atopic dermatitis. Recently, the effect of PM on healthy human skin has gained attention.
Objective:
To evaluate the relationship between PM concentration and objective skin changes in healthy subjects.
Methods:
This prospective study enrolled 25 healthy volunteers without any skin disease. Data regarding daily meteorological parameters and air pollution were collected during a high-PM period and a low-PM period for 14 days. Environmental and lifestyle factors that might influence skin conditions of subjects were also collected during the study period. Biophysical parameters of the skin such as transepidermal water loss (TEWL), hydration, erythema index, and melanin index were measured. Pores, wrinkles, sebum, and skin tone were evaluated using a facial analysis system.
Results:
Mean TEWL value during the high-PM period was significantly higher than that during the low-PM period (10.16 g/m2/h vs. 5.99 g/m2/h; p=0.0005). Mean erythema index was significantly higher in the high-PM period than that in the low-PM period (4.3 vs. 3.42; p=0.038). For facial analysis system indices, uniformity of skin tone was higher in the low-PM period than that in the high-PM period (p<0.0001). In addition, with increasing PM10 and PM2.5, TEWL also showed increase when other environmental components were constant (regression coefficient [RC]=0.1529, p<0.0001 for PM10; RC=0.2055, p=0.0153 for PM2.5).
Conclusion:
Increased PM concentrations may contribute to disturbed barrier function, increased facial erythema, and uneven skin tone even in healthy human skin.
The molecular mechanisms that underlie the detrimental effects of particulate matter (PM) on skin barrier function are poorly understood. In this study, the effects of PM2.5 on filaggrin (FLG) and skin barrier function were investigated in vitro and in vivo. The levels of FLG degradation products including pyrrolidone carboxylic acid, urocanic acid (UCA), and cis/trans UCA were significantly decreased in skin tape stripping samples of study subjects when they moved from Denver, an area with low PM2.5, to Seoul, an area with high PM2.5 count. Experimentally, PM2.5 collected in Seoul inhibited FLG, loricrin, keratin-1, desmocollin-1, and corneodesmosin, but did not modulate involucrin or claudin-1 in keratinocyte cultures. Moreover, FLG protein expression was inhibited in human skin equivalents and murine skin treated with PM2.5. We demonstrate that this process was mediated by PM2.5-induced TNF-alpha and was aryl hydrocarbon receptor-dependent. PM2.5 exposure compromised skin barrier function, resulting in increased transepidermal water loss and enhanced the penetration of FITC-dextran in organotypic and mouse skin. PM2.5-induced TNF-alpha causes FLG deficiency in the skin and subsequently induces skin barrier dysfunction. Compromised skin barrier due to PM2.5 exposure may contribute to the development and the exacerbation of allergic diseases such as AD.
Background:
Air pollution is killing close to 5 million people a year, and harming billions more. Air pollution levels remain extremely high in many parts of the world, and air pollution-associated premature deaths have been reported for urbanized areas, particularly linked to the presence of airborne nano-sized and ultrafine particles.
Main text:
To date, most of the research studies did focus on the adverse effects of air pollution on the human cardiovascular and respiratory systems. Although the skin is in direct contact with air pollutants, their damaging effects on the skin are still under investigation. Epidemiological data suggested a correlation between exposure to air pollutants and aggravation of symptoms of chronic immunological skin diseases. In this study, a systematic literature review was conducted to understand the current knowledge on the effects of airborne particulate matter on human skin. It aims at providing a deeper understanding of the interactions between air pollutants and skin to further assess their potential risks for human health.
Conclusion:
Particulate matter was shown to induce a skin barrier dysfunction and provoke the formation of reactive oxygen species through direct and indirect mechanisms, leading to oxidative stress and induced activation of the inflammatory cascade in human skin. Moreover, a positive correlation was reported between extrinsic aging and atopic eczema relative risk with increasing particulate matter exposure.
The skin exposome is defined as the totality of environmental exposures over the life course that can induce or modify various skin conditions. Here, we review the impact on the skin of solar exposure, air pollution, hormones, nutrition and psychological factors. Photoageing, photocarcinogenesis and pigmentary changes are well‐established consequences of chronic exposure of the skin to solar radiation. Exposure to traffic‐related air pollution contributes to skin ageing. Particulate matter and nitrogen dioxide cause skin pigmentation/lentigines, while ozone causes wrinkles and has an impact on atopic eczema. Human skin is a major target of hormones, and they exhibit a wide range of biological activities on the skin. Hormones decline with advancing age influencing skin ageing. Nutrition has an impact on numerous biochemical processes, including oxidation, inflammation and glycation, which may result in clinical effects, including modification of the course of skin ageing and photoageing. Stress and lack of sleep are known to contribute to a pro‐inflammatory state, which, in turn, affects the integrity of extracellular matrix proteins, in particular collagen. Hormone dysregulation, malnutrition and stress may contribute to inflammatory skin disorders, such as atopic dermatitis, psoriasis, acne and rosacea.
Accumulating evidence suggests that particulate matter (PM2.5), as a major air pollutant, imposes a certain degree of destruction and toxicity to the skin. It particularly impairs the structure and function of the epidermis. To study the impact of PM2.5 on the skin, transcriptome analysis was performed on PM2.5-exposed human primary keratinocytes. Functional annotation analysis demonstrates that PM2.5 significantly up-regulates cholesterol-metabolism-related genes. Via lipid extraction from PM2.5 treated three-dimensional epidermis tissue model (3D-ETM) and subsequent characterization via mass spectrometry, it was confirmed that PM2.5 significantly increases epidermal cholesterol levels in vitro. Conversely, the amount of squalene in 3D-ETM was significantly reduced by PM2.5. Interestingly, neither cholesterol nor squalene showed significant fluctuations in the green tea extract (GTE) treated epidermis tissue model under PM2.5 exposure. This study shows that PM2.5 may cause barrier disorders by increasing cholesterol synthesis, leading to transient accumulation of epidermal cholesterol and decrease of squalene. It was suggested that cholesterol and squalene, which are the key substances affecting skin barrier function, can be used as new biomarkers of skin damage induced by PM2.5. Moreover, it was demonstrated that GTE can reduce damage caused by PM2.5 exposure by not only anti-inflammatory and antioxidant mechanisms, but also by off-setting the disturbance to epidermal lipid homeostasis. This study demonstrates the strong potential of GTE as an active ingredient to be utilized in cosmetic products to effectively reduce the damage PM2.5 induces in skin.
The skin is the main barrier that protects us against environmental stressors (physical, chemical, and biological). These stressors, combined with internal factors, are responsible for cutaneous aging. Furthermore, they negatively affect the skin and increase the risk of cutaneous diseases, particularly skin cancer. This review addresses the impact of environmental stressors on skin aging, especially those related to general and specific external factors (lifestyle, occupation, pollutants, and light exposure). More specifically, we have evaluated ambient air pollution, household air pollutants from non-combustion sources, and exposure to light (ultraviolet radiation and blue and red light). We approach the molecular pathways involved in skin aging and pathology as a result of exposure to these external environmental stressors. Finally, we reflect on how components of environmental stress can interact with ultraviolet radiation to cause cell damage and the critical importance of knowing the mechanisms to develop new therapies to maintain the skin without damage in old age and to repair its diseases.
Endoplasmic reticulum (ER) stress is a mechanism that allows the protection of normal cellular functions in response to both internal perturbations, such as accumulation of unfolded proteins, and external perturbations, for example redox stress, UVB irradiation, and infection. A hallmark of ER stress is the accumulation of misfolded and unfolded proteins. Physiological levels of ER stress trigger the unfolded protein response (UPR) that is required to restore normal ER functions. However, the UPR can also initiate a cell death program/apoptosis pathway in response to excessive or persistent ER stress. Recently, it has become evident that chronic ER stress occurs in several diseases, including skin diseases such as Darier's disease, rosacea, vitiligo and melanoma; furthermore, it is suggested that ER stress is directly involved in the pathogenesis of these disorders. Here, we review the role of ER stress in skin function, and discuss its significance in skin diseases.
This study investigated the effects of particulate matter (PM) on human skin diseases by conducting a systematic review of existing literature and performing a meta-analysis. It considered articles reporting an original effect of PM on human skin. From among 918 articles identified, 13 articles were included for further consideration after manual screening of the articles resulted in the exclusion of articles that did not contain data, review articles, editorials, and also articles in languages other than English. Random-effects models and forest plots were used to estimate the effect of PM on the skin by Meta-Disc analysis. According to people’s reports of exposure and negative skin effects (atopic dermatitis (AD), eczema, and skin aging, etc.) due to air pollution, the summary relative risk (odds ratio) of PM10 was determined to be 0.99 (95% confidence interval (CI) 0.89-1.11) whereas PM2.5 was determined to be 1.04 (95% CI 0.96-1.12). Simultaneously, there was a different extent of impact between PM10 and PM2.5 on atopic dermatitis (AD) for those of young age: the odds ratio of PM10 and PM2.5 were 0.96 (95% CI 0.83-1.11; I2 = 62.7%) and 1.05 (95% CI 0.95-1.16; I2 = 46%), respectively. Furthermore, the results suggest an estimated increase of disease incidence per 10 µg/m3 PM of 1.01% (0.08-2.05) due to PM10 and 1.60% (0.45-2.82) due to PM2.5. Following the results, PM10 and PM2.5 are associated with increased risks of human skin diseases, especially AD, whose risk is higher in infants and school children. With its smaller size and a high concentration of metals, PM2.5 is more closely related to AD in younger people, compared to PM10.
Stratum corneum forms the UV barrier. The effect of ultraviolet B (UVB) on normal skin was extensively studied; however, its effect on barrier perturbed skin remains undefined. Both barrier perturbation and UVB irradiation induce endoplasmic reticulum (ER) stress and unfolded protein response (UPR) in keratinocytes. Mild ER stress activates homeostatic UPR, while severe ER stress leads to abnormal UPR, promoting apoptosis and inflammation. Here, we investigated UV sensitivity and UVB-induced UPR in barrier-disrupted human skin and the effects of pseudoceramide-dominant emollient on UVB-induced skin responses. Tape-stripped skin of healthy volunteers showed enhanced susceptibility to erythema and augmented proinflammatory cytokines induction following suberythemal UVB irradiation. Suberythemal UVB activated XBP1 in normal skin, while increased CHOP transcription in barrier perturbed skin. After tape stripping, pseudoceramide-dominant emollient was applied for 3 days, and then, the areas were irradiated with suberythemal UVB. Pretreatment with topical pseudoceramide protected against UVB-induced upregulation of IL-1β, IL-6, and TNF-α transcription and reduced susceptibility to erythema following UVB. Topical pseudoceramide also suppressed suberythemal UVB-induced CHOP transcription in barrier-disrupted skin. Taken together, these data indicate that permeability barrier disruption increases UV sensitivity in human skin, partly via switch the UVB-induced UPR, from homeostatic signals to pro-apoptotic and proinflammatory signals. In addition, we conclude that pseudoceramide-dominant emollient suppresses excessive ER stress induction and CHOP activation following UVB in barrier damaged skin, providing evidence that pseudoceramide-dominant emollients can be promising strategies for photoprotection of the barrier damaged skin.
We explored the regulation of filaggrin, cyclooxygenase 2 (COX2) and prostaglandin E2 (PGE2) expression induced by urban particulate matter (PM) in human keratinocytes. In addition, we investigated the signaling pathways involved in PM-induced effects on COX2/PGE2 and filaggrin. PMs induced increases in COX2 expression and PGE2 production, and decreased filaggrin expression. These effects were attenuated by pretreatment with COX2 inhibitor and PGE2 receptor antagonist, or after transfection with siRNAs of the aryl hydrocarbon receptor (AhR), gp91phox and p47phox. Furthermore, PM-induced generation of reactive oxygen species (ROS) and NADPH oxidase activity was attenuated by pretreatment with an AhR antagonist (AhRI) or antioxidants. Moreover, Nox-dependent ROS generation led to phosphorylation of ERK1/2, p38, and JNK, which then activated the downstream molecules NF-κB and AP-1, respectively. In vivo studies in PMs-treated mice showed that AhRI and apocynin (a Nox2 inhibitor) had anti-inflammatory effects by decreasing COX2 and increasing filaggrin expression. Our results reveal for the first time that PMs-induced ROS generation is mediated through the AhR/p47 phox/NADPH oxidase pathway, which in turn activates ERK1/2, p38/NF-κB and JNK/AP-1, and which ultimately induces COX2 expression and filaggrin downregulation. Up-regulated expression of COX2 and production of PGE2 may lead to impairment of skin barrier function.
To investigate the facial cues by which one recognizes that someone is sleep deprived versus not sleep deprived.
Experimental laboratory study.
Karolinska Institutet, Stockholm, Sweden.
Forty observers (20 women, mean age 25 ± 5 y) rated 20 facial photographs with respect to fatigue, 10 facial cues, and sadness. The stimulus material consisted of 10 individuals (five women) photographed at 14:30 after normal sleep and after 31 h of sleep deprivation following a night with 5 h of sleep.
Ratings of fatigue, fatigue-related cues, and sadness in facial photographs.
The faces of sleep deprived individuals were perceived as having more hanging eyelids, redder eyes, more swollen eyes, darker circles under the eyes, paler skin, more wrinkles/fine lines, and more droopy corners of the mouth (effects ranging from b = +3 ± 1 to b = +15 ± 1 mm on 100-mm visual analog scales, P < 0.01). The ratings of fatigue were related to glazed eyes and to all the cues affected by sleep deprivation (P < 0.01). Ratings of rash/eczema or tense lips were not significantly affected by sleep deprivation, nor associated with judgements of fatigue. In addition, sleep-deprived individuals looked sadder than after normal sleep, and sadness was related to looking fatigued (P < 0.01).
The results show that sleep deprivation affects features relating to the eyes, mouth, and skin, and that these features function as cues of sleep loss to other people. Because these facial regions are important in the communication between humans, facial cues of sleep deprivation and fatigue may carry social consequences for the sleep deprived individual in everyday life.
Sundelin T; Lekander M; Kecklund G; Van Someren EJW; Olsson A; Axelsson J. Cues of fatigue: effects of sleep deprivation on facial appearance. SLEEP 2013;36(9):1355-1360.
PERK and IRE1 are type-I transmembrane protein kinases that reside in the
endoplasmic reticulum (ER) and transmit stress signals in response to perturbation
of protein folding. Here we show that the lumenal domains of these two proteins
are functionally interchangeable in mediating an ER stress response and that,
in unstressed cells, both lumenal domains form a stable complex with the ER
chaperone BiP. Perturbation of protein folding promotes reversible dissociation
of BiP from the lumenal domains of PERK and IRE1. Loss of BiP correlates with
the formation of high-molecular-mass complexes of activated PERK or IRE1,
and overexpression of BiP attenuates their activation. These findings are
consistent with a model in which BiP represses signalling through PERK and
IRE1 and protein misfolding relieves this repression by effecting the release
of BiP from the PERK and IRE1 lumenal domains.
For decades, extrinsic skin aging has been known to result from chronic exposure to solar radiation and, more recently, to tobacco smoke. In this study, we have assessed the influence of air pollution on skin aging in 400 Caucasian women aged 70-80 years. Skin aging was clinically assessed by means of SCINEXA (score of intrinsic and extrinsic skin aging), a validated skin aging score. Traffic-related exposure at the place of residence was determined by traffic particle emissions and by estimation of soot in fine dust. Exposure to background particle concentration was determined by measurements of ambient particles at fixed monitoring sites. The impact of air pollution on skin aging was analyzed by linear and logistic regression and adjusted for potential confounding variables. Air pollution exposure was significantly correlated to extrinsic skin aging signs, in particular to pigment spots and less pronounced to wrinkles. An increase in soot (per 0.5 × 10(-5) per m) and particles from traffic (per 475 kg per year and square km) was associated with 20% more pigment spots on forehead and cheeks. Background particle pollution, which was measured in low residential areas of the cities without busy traffic and therefore is not directly attributable to traffic but rather to other sources of particles, was also positively correlated to pigment spots on face. These results indicate that particle pollution might influence skin aging as well.
The unfolded protein response (UPR), which is induced by stress to the endoplasmic reticulum (ER), is involved in the functional alteration of certain cells, such as the differentiation of B cells to plasma cells. The aim of this study is to determine whether the UPR is activated during epidermal keratinocyte (KC) differentiation. Here, we show that the expression of the UPR-induced proteins Bip/GRP78 and HRD1 was increased in cells in the supra-basal layers of normal human epidermis that contain KCs undergoing differentiation as well as in skin-equivalent cultured KCs. However, Bip/GRP78 and HRD1 were poorly expressed in proliferating KCs in squamous cell carcinoma and psoriasis vulgaris tissues. The epidermal growth factor receptor tyrosine kinase inhibitor, PD153035, which induces KC differentiation, upregulated UPR-induced marker mRNAs and proteins. Furthermore, microarray analyses and quantitative PCR revealed that ER stress-inducing reagents, tunicamycin (TU), thapsigargin, and brefeldin A, altered the expression of genes essential for human epidermal KC differentiation, including C/EBPbeta, KLF4, and ABCA12 in vitro. However, ABCA12 and KLF4 mRNA did not increase with TU treatment after siRNA-mediated knockdown of XBP-1. Taken together, our findings strongly suggest that the UPR is activated during normal epidermal KC differentiation and induces C/EBPbeta, KLF4, and ABCA12 mRNAs.
b> Background: The anatomic layers of the skin are well-defined, and a functional model of the skin barrier has recently been described. Barrier disruption plays a key role in several skin conditions, and moisturization is recommended as an initial treatment in conditions such as atopic dermatitis. This review aimed to analyze the skin barrier in the context of the function model, with a focus on the mechanisms by which moisturizers support each of the functional layers of the skin barrier to promote homeostasis and repair. Summary: The skin barrier is comprised of four interdependent layers – physical, chemical, microbiologic, and immunologic – which maintain barrier structure and function. Moisturizers target disruption affecting each of these four layers through several mechanisms and were shown to improve transepidermal water loss in several studies. Occlusives, humectants, and emollients occlude the surface of the stratum corneum (SC), draw water from the dermis into the epidermis, and assimilate into the SC, respectively, in order to strengthen the physical skin barrier. Acidic moisturizers bolster the chemical skin barrier by supporting optimal enzymatic function, increasing ceramide production, and facilitating ideal conditions for commensal microorganisms. Regular moisturization may strengthen the immunologic skin barrier by reducing permeability and subsequent allergen penetration and sensitization. Key Messages: The physical, chemical, microbiologic, and immunologic layers of the skin barrier are each uniquely impacted in states of skin barrier disruption. Moisturizers target each of the layers of the skin barrier to maintain homeostasis and facilitate repair.
It is widely known that lack of sleep damages the skin. Therefore, it is necessary to explore the relationship between sleep deprivation and skin damage and to find effective treatments. We established a 28-day sleep restriction (SR) mice model simulating continuous long-term sleep loss. We found that SR would damage the barrier function of mice's skin, cause oxidative stress damage to the skin, weaken the oscillations of the skin's biological clock, and make the circadian rhythm of Bacteroides disappear. The circadian rhythm of short-chain fatty acids (SCFA) receptors in the skin was disordered. After melatonin supplementation, the skin damage caused by SR was improved, the oscillations of the biological clock were enhanced, the circadian rhythm of Bacteroides was restored, and the rhythm of the receptor GPR43 of propionic acid was restored. We speculated that the improving effect of melatonin may be mediated by propionic acid produced by the gut microbiota. We verified in vitro that propionic acid could improve the keratinocytes barrier function of oxidative damage. We then consumed the gut microbiota of mice through antibiotics and found that oral melatonin could not improve skin damage. Moreover, supplementing mice with propionic acid could improve skin damage. Our research showed that lack of sleep impaired skin barrier function. Oral melatonin could improve skin damage by restoring the circadian rhythm of Bacteroides and its propionic acid metabolite. This article is protected by copyright. All rights reserved.
Pollution in the world and exposure of humans and nature to toxic substances is continuously worsening at a rapid pace. In the last 60 years, human and domestic animal health has been challenged by continuous exposure to toxic substances and pollutants because of uncontrolled growth, modernization, and industrialization. More than 350,000 new chemicals have been introduced to our lives, mostly without any reasonable control of their health effects and toxicity. A plethora of studies show exposure to these harmful substances during this period with their implications on the skin and mucosal epithelial barrier and increasing prevalence of allergic and autoimmune diseases in the context of the "epithelial barrier hypothesis". Exposure to these substances causes an epithelial injury with peri-epithelial inflammation, microbial dysbiosis and bacterial translocation to sub-epithelial areas, and immune response to dysbiotic bacteria. Here, we provide scientific evidence on the altered human exposome and its impact on epithelial barriers.
Background
Endoplasmic reticulum (ER) calcium depletion-induced ER stress is a crucial signal for keratinocyte differentiation and barrier homeostasis, but its effects on the epidermal tight junction (TJ) have not been characterized. Ultraviolet B (UVB) causes ER calcium release in keratinocytes and disrupts epidermal TJ, however, the involvement of ER stress in the UVB-induced TJ alterations remains unknown.
Objectives
To investigate the effect of ER stress by pharmacological ER calcium depletion or UVB on the TJ integrity in normal human epidermal keratinocytes (NHEK).
Methods
NHEK were exposed to ER calcium pump inhibitor thapsigargin (Tg) or UVB. ER stress markers and TJ molecules expression, TJ and F-actin structures, and TJ barrier function were analyzed.
Results
Tg or UVB exposure dose-dependently triggered unfolded protein response (UPR) in NHEK. Low dose Tg induced the IRE1α-XBP1 pathway and strengthened TJ barrier. Contrary, high dose Tg activated PERK phosphorylation and disrupted TJ by F-actin disorganization. UVB disrupted TJ and F-actin structures dose dependently. IRE1α RNase inhibition induced or exacerbated TJ and F-actin disruption in the presence of low dose Tg or UVB. High dose Tg increased RhoA activity. 4-PBA or Rho kinase (ROCK) inhibitor partially prevented the disruption of TJ and F-actin following high dose Tg or UVB.
Conclusions
ER stress has bimodal effects on the epidermal TJ depending on its intensity. The IRE1α pathway is critical for the maintenance of TJ integrity during mild ER stress. Severe ER stress-induced UPR or ROCK signalling mediates the disruption of TJ through cytoskeletal disorganization during severe ER stress.
The skin is the outermost layer of the body with an extensive surface area of approximately 1.8 m2, is the first line of defence against a multitude of external pathogens and environmental insults. The skin also has important homeostatic functions such as reducing water loss and contributing to thermoregulation of the body. The structure of the skin and cellular composition work in harmony to prevent infection, deal with physical and chemical challenges from the outside World. In this review we discuss how the structural cells such as keratinocytes, fibroblasts and adipocytes contribute to barrier immunity. We also discuss specialised immune cells that are resident in steady‐state skin such as mononuclear phagocytes such as Langerhans cells, dermal macrophages and dermal dendritic cells in addition to the resident memory T cells. Ageing results in increase in skin infections and increased cancer incidence. As we age the skin structure changes with thinning of the epidermis and dermis, increased water loss and fragmented collagen and elastin. In addition the skin immune composition changes with reduced Langerhans cells, decreased antigen‐specific immunity and increased regulatory populations such as Foxp3+ Tregs. Together, these alterations result in decreased barrier immunity in the elderly explain in part their increased susceptible to cancer and infections.
Background:
Previous studies have demonstrated increased pore size and darkening skin color with total sleep deprivation. There are many studies of skin characteristics with short-term sleep restriction, but there are few studies on skin characteristics when sleep is restricted more than three consecutive days. This study evaluated skin changes with sleep limited to 4 hours per night for six nights.
Materials and methods:
The study included 32 Korean women in their 40s. Skin hydration, desquamation, barrier recovery, texture, gloss, transparency, elasticity, crow's feet, frown lines, and color were measured. Individual sleep time was monitored by smartwatches. Subjects slept 8 hours per night for six nights in week one and 4 hours per night for six nights in week two.
Results:
Skin hydration was significantly reduced after 1 day of sleep deprivation, and it continued to decrease. Skin gloss, desquamation, transparency, elasticity, and wrinkles were significantly aggravated after 1 day of sleep deprivation. Skin texture was significantly aggravated on the fourth day of sleep restriction. Elasticity was most affected by reduced sleep, with a standardized coefficient of -.320, indicating a significant decrease over time as compared to other characteristics.
Conclusion:
Skin hydration was gradually decreased with sleep restriction. Skin texture did not change after only 1 day of sleep restriction. It is a new finding that elasticity decreases more than other skin characteristics with prolonged sleep restriction.
Background
The skin exposome refers to the constellation of external exposures that contribute to cutaneous aging, including solar radiation, air pollution, tobacco smoke, unbalanced nutrition, and cosmetic products. This review explores the skin exposome and the role of a combination hyaluronic acid and mineralized thermal water product used to restore and maintain optimal skin barrier function.
Method
An expert panel of 7 dermatologists who treat clinical signs of facial aging convened for a one‐day meeting to discuss the results of a literature review on the skin exposome and the role of M89, a mineralized thermal water and hyaluronic acid‐based gel, to improve the quality of facial skin. Evidence coupled with expert opinion and experience of the panel was used to address clinical challenges in the treatment of photo‐aging, and the use of M89.
Results
Solar radiation (ultraviolet radiation, visible light, and infrared radiation), air pollution, tobacco smoke, nutrition, and miscellaneous factors, including stress, sleep deprivation, and temperature, may potentiate skin aging by triggering molecular processes that damage skin structure. M89 was developed to maintain and restore skin and contains ingredients to aid physical, hydric, antioxidant, and antimicrobial skin barrier function.
Conclusions
Increasing knowledge of the exposome and microenvironment contributing to skin aging may support a better understanding of measures to support the skin. The initial results of in vitro and clinical studies of M89 show its potential to improve skin barrier function.
Background:
Particulate matter (PM) is an integral part of air pollution, which is a mixture of particles suspended in the air. Recently, it has been reported that PM is associated with increased risks of skin diseases, especially atopic dermatitis in children. However, it is unclear if PM directly goes into the skin and what mechanisms are involved in response to PM.
Objective:
To see whether PM could penetrate into the barrier-disrupted skin, produce reactive oxygen species (ROS), and elicit an inflammatory response.
Methods:
We collected PMs during a winter in Seoul and used cultured keratinocytes for in vitro study and tape-stripped BALB/c mice for in vivo study.
Results:
Keratinocyte cytotoxicity increased in a dose-dependent manner by PM treatment. IL-8 and MMP-1 mRNA expression and protein levels were significantly increased compared to control by qPCR and ELISA, respectively. Cellular ROS production was increased by PM treatment, and antioxidant N-acetyl cysteine pretreatment prevented induction of inflammatory cytokines IL-8 and MMP-1. In PM-treated keratinocytes, electron-dense subcellular particles were observed by transmission electron microscopy. PM was observed inside hair follicles in both intact and barrier-disrupted skin in vivo. Additionally, intercellular penetration of PM was seen in the barrier-disrupted skin. Repeated PM application induced epidermal thickening and dermal inflammation with neutrophil infiltration. Finally, N-acetyl cysteine could ameliorate skin inflammation induced by PM application.
Conclusion:
PM penetrates into the barrier-disrupted skin, causing inflammation, demonstrating detrimental effects in the skin.
Background
Sleep is important for growth and renewal of multiple physiological systems. The effects of chronic poor sleep quality on human skin function and visible signs of ageing have not been elucidated.AimTo evaluate the effect of chronic poor sleep quality on measures of skin health and ageing. Self-perceived satisfaction with appearance was also assessed.Methods60 healthy caucasian women, who were categorized as poor quality sleepers [Pittsburg Sleep Quality Index (PSQI) > 5, sleep duration ≤ 5 h] or good quality sleepers (PSQI ≤ 5, sleep duration 7–9 h). A validated clinical tool, SCINEXATM, was used to assess intrinsic and extrinsic skin ageing. Dark under-eye circles were evaluated using standardized photos. Measurement of in vivo transepidermal water loss (TEWL) was used to assess recovery of the skin barrier after tape stripping. Subjects were exposed to simulated solar ultraviolet light, and recovery from erythema was monitored. Subjects also completed a questionnaire evaluating self-perception of attractiveness.ResultsGood sleepers had significantly lower intrinsic skin ageing scores by SCINEXATM. At baseline, poor sleepers had significantly higher levels of TEWL. At 72 h after tape stripping, good sleepers had 30% greater barrier recovery compared with poor sleepers. At 24 h after exposure to ultraviolet light, good sleepers had significantly better recovery from erythema. Good sleepers also reported a significantly better perception of their appearance and physical attractiveness compared with poor sleepers.Conclusions
This study indicates that chronic poor sleep quality is associated with increased signs of intrinsic ageing, diminished skin barrier function and lower satisfaction with appearance.
Recent scientific interest in the pathogenesis of rosacea focuses on abnormally high facial skin levels of cathelicidin and the trypsin-like serine protease kallikrein 5 (KLK5) that cleaves the cathelicidin precursor protein into the bioactive fragment LL-37, which exerts crucial proinflammatory, angiogenic and antimicrobial activities. Furthermore, increased expression of Toll-like receptor-2 (TLR2) has been identified in rosacea skin supporting the participation of the innate immune system. Notably, TLRs are expressed on sensory neurons and increase neuronal excitability linking TLR signaling to the transmission of neuroinflammatory responses. It is the intention of this viewpoint to present a unifying concept that links all known clinical trigger factors of rosacea such as UV-irradiation, heat, skin irritants, and special foods to one converging point: enhanced endoplasmic reticulum (ER)-stress that activates the unfolded protein response (UPR). ER-stress via upregulation of transcription factor ATF4 increases TLR2 expression resulting in enhanced production of cathelicidin and KLK5 mediating downstream proinflammatory, angiogenic and antimicrobial signaling. The presented concept identifies rosacea trigger factors as environmental stressors that enhance the skin′s ER-stress response. Exaggerated cutaneous ER-stress that stimulates the TLR2-driven inflammatory response may involve sebocytes, keratinocytes, monocyte-macrophages and sensory cutaneous neurons. Finally, all anti-rosacea drugs are proposed to attenuate the ER-stress signaling cascade at some point. Over-stimulated ER-stress signaling may have evolutionarily evolved as a compensatory mechanism to balance impaired vitamin D-driven LL-37-mediated antimicrobial defenses due to lower exposure of UV-B irradiation of the Northern Celtic population.This article is protected by copyright. All rights reserved.
The endoplasmic-reticulum (ER) stress response constitutes a cellular process that is triggered by a variety of conditions that disturb folding of proteins in the ER. Eukaryotic cells have developed an evolutionarily conserved adaptive mechanism, the unfolded protein response (UPR), which aims to clear unfolded proteins and restore ER homeostasis. In cases where ER stress cannot be reversed, cellular functions deteriorate, often leading to cell death. Accumulating evidence implicates ER stress-induced cellular dysfunction and cell death as major contributors to many diseases, making modulators of ER stress pathways potentially attractive targets for therapeutics discovery. Here, we summarize recent advances in understanding the diversity of molecular mechanisms that govern ER stress signaling in health and disease. This article is part of a Special Issue entitled: Cell Death Pathways.
Protein-folding stress at the endoplasmic reticulum (ER) is a salient feature of specialized secretory cells and is also involved in the pathogenesis of many human diseases. ER stress is buffered by the activation of the unfolded protein response (UPR), a homeostatic signalling network that orchestrates the recovery of ER function, and failure to adapt to ER stress results in apoptosis. Progress in the field has provided insight into the regulatory mechanisms and signalling crosstalk of the three branches of the UPR, which are initiated by the stress sensors protein kinase RNA-like ER kinase (PERK), inositol-requiring protein 1α (IRE1α) and activating transcription factor 6 (ATF6). In addition, novel physiological outcomes of the UPR that are not directly related to protein-folding stress, such as innate immunity, metabolism and cell differentiation, have been revealed.
Modern society has reported a decline in sleep time in the recent decades. This reduction can increase the morbidity and mortality of several diseases and leads to an immunosuppressive state. The skin is the largest organ in the human body and collagen, its main component, has a key role in the structure and integrity of the organism. The entire sequence of events necessary during collagen formation can be affected by endogenous and exogenous factors. A variety of studies in the literature have shown that sleep plays a role in restoring immune system function and that changes in the immune response may affect collagen production. Several studies of prolonged sleep deprivation suggest a break in skin barrier function and mucous membranes. In fact, the reduction of sleep time affects the composition and integrity of various systems. Thus, we hypothesized that lack of sleep as well as other types of stress can impair skin integrity.
Despite clear exacerbation of several skin disorders by stress, the effect of psychologic or exertional stress on human skin has not been well studied. We investigated the effect of three different stressors, psychologic interview stress, sleep deprivation, and exercise, on several dermatologic measures: transepidermal water loss, recovery of skin barrier function after tape stripping, and stratum corneum water content (skin conductance). We simultaneously measured the effects of stress on plasma levels of several stress-response hormones and cytokines, natural killer cell activity, and absolute numbers of peripheral blood leukocytes. Twenty-five women participated in a laboratory psychologic interview stress, 11 women participated in one night of sleep deprivation, and 10 women participated in a 3 d exercise protocol. The interview stress caused a delay in the recovery of skin barrier function, as well as increases in plasma cortisol, norepinephrine, interleukin-1beta and interleukin-10, tumor necrosis factor-alpha, and an increase in circulating natural killer cell activity and natural killer cell number. Sleep deprivation also decreased skin barrier function recovery and increased plasma interleukin-1beta, tumor necrosis factor-alpha, and natural killer cell activity. The exercise stress did not affect skin barrier function recovery, but caused an increase in natural killer cell activity and circulating numbers of both cytolytic T lymphocytes and helper T cells. In addition, cytokine responses to the interview stress were inversely correlated with changes in barrier function recovery. These results suggest that acute psychosocial and sleep deprivation stress disrupts skin barrier function homeostasis in women, and that this disruption may be related to stress-induced changes in cytokine secretion.
The sequencing and mapping of the human genome provides a foundation for the elucidation of gene expression and protein function, and the identification of the biochemical pathways implicated in the natural history of chronic diseases, including cancer, diabetes, and vascular and neurodegenerative
Proteins synthesized in the endoplasmic reticulum (ER) are properly folded with the assistance of ER chaperones. Malfolded proteins are disposed of by ER-associated protein degradation (ERAD). When the amount of unfolded protein exceeds the folding capacity of the ER, human cells activate a defense mechanism called the ER stress response, which induces expression of ER chaperones and ERAD components and transiently attenuates protein synthesis to decrease the burden on the ER. It has been revealed that three independent response pathways separately regulate induction of the expression of chaperones, ERAD components, and translational attenuation. A malfunction of the ER stress response caused by aging, genetic mutations, or environmental factors can result in various diseases such as diabetes, inflammation, and neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, and bipolar disorder, which are collectively known as 'conformational diseases'. In this review, I will summarize recent progress in this field. Molecules that regulate the ER stress response would be potential candidates for drug targets in various conformational diseases.