[show abstract][hide abstract] ABSTRACT: Entamoeba histolytica is an extracellular tissue parasite causing colitis and occasional liver abscess in humans. E. histolytica-derived secretory products (SPs) contain large amounts of cysteine proteases (CPs), one of the important amoebic virulence factors. Although tissue-residing mast cells play an important role in the mucosal inflammatory response to this pathogen, it is not known whether the SPs induce mast cell activation. In this study, when human mast cells (HMC-1 cells) were stimulated with SPs collected from pathogenic wild-type amoebae, interleukin IL-8 mRNA expression and production were significantly increased compared with cells incubated with medium alone. Inhibition of CP activity in the SPs with heat or the CP inhibitor E64 resulted in significant reduction of IL-8 production. Moreover, SPs obtained from inhibitors of cysteine protease (ICP)-overexpressing amoebae with low CP activity showed weaker stimulatory effects on IL-8 production than the wild-type control. Preincubation of HMC-1 cells with antibodies to human protease-activated receptor 2 (PAR2) did not affect the SP-induced IL-8 production. These results suggest that cysteine proteases in E. histolytica-derived secretory products stimulate mast cells to produce IL-8 via a PAR2-independent mechanism, which contributes to IL-8-mediated tissue inflammatory responses during the early phase of human amoebiasis.
[show abstract][hide abstract] ABSTRACT: To investigate whether low vitamin D status was related to insulin resistance (IR) or impaired fasting glucose (IFG) in Korean adolescents, after adjusting for total body fat mass (FM).
A cross-sectional study.
Korea National Health and Nutrition Examination Survey (KNAHNES) 2009-2010.
In total, 1466 participants (769 males) aged 10-19 years were assessed for serum 25-hydroxyvitamin D (25(OH)D) levels, for FM by whole-body dual-energy X-ray absorptiometry and for IR by homeostasis model assessment (HOMA-IR) after an 8 h fast.
Age-, sex-, season- and physical-activity-adjusted regression models showed that serum 25(OH)D levels were significantly related to markers of adiposity (P = 0·016 for FM (g), P = 0·023 for FM (%) and P = 0·035 for fat mass index). When the participants were stratified into three 25(OH)D categories (<37·5 nmol/l (n 553), 37·5 to < 50 nmol/l (n 543) and ≥ 50 nmol/l (n 370)), significantly decreasing trends were observed for fasting insulin (all P < 0·001), HOMA-IR (all P < 0·001) and the odds ratios for IFG (all P for trend < 0·05) from the lowest to the highest 25(OH)D category, after adjustments for age, sex, physical activity and all markers of adiposity. In the multivariate logistic regression analysis, the likelihood of participants in the lowest serum 25(OH)D category having IFG was 2·96-3·15 compared with those in the highest 25(OH)D category (all P < 0·05).
There was a significant inverse relationship between vitamin D status and IR and the risk of IFG, independent of adiposity, in Korean adolescents.
Public Health Nutrition 09/2013; · 2.25 Impact Factor
[show abstract][hide abstract] ABSTRACT: Adult neurogenesis can be influenced by a variety of factors. Stress is one of the most potent inhibitors of hippocampal neurogenesis. Stress effects on adult hippocampal neurogenesis are affected differently by environmental factors, including social interaction. Sexual behavior between males and females in a social context has been suggested to influence neurogenesis and enhance hippocampal cell proliferation. However, the mechanisms of action of sexual interaction, the possible changes relative to stress state, and its effects on learning and memory remain uncertain. The current study examined the influence of sexual interaction on neurological responses in adult male mice and the function of sexual interaction relative to recognition memory in stress states. Changes in the expression of neurotrophic and transcription factors were assessed in reference to stress and/or sexual behaviors. The survival of newly generated cells and their rate of differentiation into neurons were determined in the hippocampus of chronically stressed and/or sexually experienced mice. Finally, to evaluate whether sexual experience alters adult hippocampal function, we tested learning and memory in a recognition memory task. The results demonstrated that sexual activity increased the expression of brain-derived neurotrophic factor, tyrosine kinase B, and cAMP response element-binding factor. Furthermore, the results supported the view that sexual interaction could be helpful for buffering adult hippocampal neurogenesis and recognition memory function against the suppressive actions of chronic stress.
[show abstract][hide abstract] ABSTRACT: Obesity and its related factors are known to suppress the secretion of growth hormone (GH). We aimed to evaluate the influence of body mass index (BMI) on the peak GH response to provocative testing in short children without GH deficiency. We conducted a retrospective review of medical records of 88 children (2-15 yr old) whose height was less than 3 percentile for one's age and sex, with normal results (peak GH level > 10 ng/mL) of GH provocative testing with clonidine and dopamine. Peak stimulated GH level, height, weight, pubertal status and serum IGF-1 level were measured. Univariate analysis showed that the BMI standard deviation score (SDS) correlated negatively with the natural log (ln) of the peak stimulated GH level (ln peak GH). BMI SDS did not correlate significantly with sex, age, pubertal status, or ln IGF-1 level. BMI SDS correlated negatively with ln peak GH level induced by clonidine but not by dopamine. In stepwise multivariate regression analysis, BMI SDS was the only significant predictor of ln peak GH level in the combination of tests and the clonidine test, but not in the dopamine test. In children without GH deficiency, BMI SDS correlates negatively with the peak GH level. BMI SDS should be included in the analysis of the results of GH provocation tests, especially tests with clonidine.
Journal of Korean medical science 09/2013; 28(9):1351-5. · 0.84 Impact Factor
[show abstract][hide abstract] ABSTRACT: Intracranial germ cell tumors (GCTs) frequently take an insidious clinical course before diagnosis. To date, clinical latency has been discussed in the context of germinoma in the suprasellar area and basal ganglia.
In this study, we classified the clinical latency of intracranial GCTs into three categories and described their characteristics in order to understand the full spectrum of the phenomenon.
In a cohort of 181 patients with intracranial GCTs, 17 patients had a delayed diagnosis of more than 3 months (90 days) from the initial brain magnetic resonance imaging to the definitive GCT diagnosis. Clinical records and radiological data of the patients were reviewed.
The patients with a delayed diagnosis were categorized into three groups according to their tumor location: suprasellar (nine patients), basal ganglia (six patients), and pineal (two patients). Initial symptomatology corresponded with the tumor location: central diabetes insipidus for the suprasellar group, hemiparesis for the basal ganglia group, and precocious puberty for the pineal group. The overall survival of patients with germinoma and delayed diagnosis was significantly shorter than that of patients who were diagnosed within 3 months (P = 0.002).
Clinical latency and delayed diagnosis are not restricted to germinomas in the suprasellar area and basal ganglia; they are canonical features of intracranial GCTs including pineal non-germinomatous GCTs. Early detection and proactive diagnosis of these tumors are required because diagnosis delay may negatively influence patient survival.
Child s Nervous System 06/2013; · 1.24 Impact Factor
[show abstract][hide abstract] ABSTRACT: Severe obesity is a major problem in pediatric craniopharyngioma. We investigated whether tumor origin, growth pattern, and surgical damage predict obesity in pediatric craniopharyngioma. Subjects were 58 patients (30 males) with no tumor recurrence during the first postoperative 18 months. Preoperative hypothalamic involvement was classified into no (pre_G0, n = 19), little (pre_G1, n = 21), and severe (pre_G2, n = 18) involvement groups based on sub- or supradiaphragmatic tumor origin and growth patterns. Postoperative hypothalamic involvement was classified into no (post_G0, n = 4), minimal (post_G1, n = 19), and significant (post_G2, n = 35) involvement groups according to follow-up imaging. The prevalence of obesity increased from 13.2 % at diagnosis (mean age = 8.1 years) to 37.9 % at last follow-up (mean duration = 9.1 years). Only the body mass index (BMI) Z-score increment of the first postoperative year (first-year ΔBMI_Z) was significant (P = 0.007). Both the preoperative BMI_Z (P = 0.001) and the first-year ΔBMI_Z (P = 0.017) showed an increasing trend from the pre_G0 to pre_G1 to pre_G2 group. For the 40 patients with pre_G0 or pre_G1, the first-year ΔBMI_Z was higher in the post_G2 group than the post_G1 group (0.02 ± 0.91 vs. 0.89 ± 0.72, P = 0.003). Tumor origin and growth pattern affect preoperative BMI_Z and postoperative weight gain. Despite little or no hypothalamic involvement at diagnosis, surgical damage contributes to postoperative weight gain in patients with craniopharyngioma.
Journal of Neuro-Oncology 04/2013; · 3.12 Impact Factor
[show abstract][hide abstract] ABSTRACT: OBJECTIVE: To evaluate the prevalence of vitamin D deficiency and predictors for low vitamin D status in Korean adolescents living between latitudes 33° and 39°N. DESIGN: A descriptive cross-sectional study. SETTING: Korea National Health and Nutrition Examination Survey (KNHANES) 2008-2009. SUBJECTS: A total of 1510 healthy adolescents aged 12-18 years (806 male, mean age 14·7 years) participated. Possible predictors for low vitamin D status (log-transformed 25-hydroxyvitamin D (25(OH)D) concentrations) were evaluated. RESULTS: The prevalence of vitamin D deficiency (25(OH)D<20 ng/ml) was 89·1 % in spring, 53·7 % in summer, 63·9 % in autumn and 90·5 % in winter. Winter season, older age, higher education level reached, being female, being obese, a lack of vitamin D supplementation, lower milk consumption (0-<200 ml/d) and a lack of physical activity were unadjusted predictors (all P < 0·05). Multiple linear regression analysis showed that winter season (P < 0·001), higher education level (P < 0·001) and a lack of vitamin D supplementation (P = 0·012) were independent predictors for low vitamin D status. The modifying effect of season on the association between vitamin D supplement use and vitamin D status was significant (P < 0·001). CONCLUSIONS: Vitamin D deficiency was highly prevalent in Korean adolescents, especially those in higher school grades. Vitamin D supplementation may contribute to maintain a better vitamin D status with lower seasonal variation. Further studies are required to determine optimal vitamin D intakes to maintain sufficient vitamin D status for Korean adolescents.
Public Health Nutrition 03/2013; · 2.25 Impact Factor
[show abstract][hide abstract] ABSTRACT: , which causes amoebic colitis and occasionally liver abscess in humans, is able to induce host cell death. However, signaling mechanisms of colon cell death induced by are not fully elucidated. In this study, we investigated the signaling role of NOX in cell death of HT29 colonic epithelial cells induced by . Incubation of HT29 cells with amoebic trophozoites resulted in DNA fragmentation that is a hallmark of apoptotic cell death. In addition, generate intracellular reactive oxygen species (ROS) in a contact-dependent manner. Inhibition of intracellular ROS level with treatment with DPI, an inhibitor of NADPH oxidases (NOXs), decreased -induced ROS generation and cell death in HT29 cells. However, pan-caspase inhibitor did not affect -induced HT29 cell death. In HT29 cells, catalytic subunit NOX1 and regulatory subunit Rac1 for NOX1 activation were highly expressed. We next investigated whether NADPH oxidase 1 (NOX1)-derived ROS is closely associated with HT29 cell death induced by . Suppression of Rac1 by siRNA significantly inhibited -induced cell death. Moreover, knockdown of NOX1 by siRNA, effectively inhibited -triggered DNA fragmentation in HT29 cells. These results suggest that NOX1-derived ROS is required for apoptotic cell death in HT29 colon epithelial cells induced by .
The Korean Journal of Parasitology 02/2013; 51(1):61-8. · 0.88 Impact Factor
[show abstract][hide abstract] ABSTRACT: The dietary reference intake (DRI) of vitamin D for Korean children was reduced from 400 IU/day in 2005 to 200 IU/day in 2010. We evaluated the risk factors for low 25-hydroxyvitamin D [25(OH)D] status and its relationships with bone health in peripubertal nonobese children living in Seoul or Gyeonggi-do. One hundred children (9.3 ± 1.9 years, 71 prepubertal, 45 boys) participated in the winter (n = 38, December through March) and summer (June through September). Bone mineral content (Z_BMC), fat mass (Z_FM), lean mass (Z_LM), and bone mineral density for the total body (Z_TB) and lumbar spine (Z_L1-4) were measured using dual-energy X-ray absorptiometry. Twenty-nine percent of children (47.4 % in winter, 17.7 % in summer) were vitamin D deficient (25(OH)D level of <20 ng/mL). The winter season (P = 0.008) and low vitamin D intake (P = 0.044) were associated with low 25(OH)D level. The 25(OH)D level correlated positively with Z_BMC (P = 0.040), Z_TB (P = 0.027), and Z_L1-4 (P = 0.045) independently of sex, puberty, Z_FM, Z_LM, physical activity level, and calcium intake. Z_FM correlated independently with Z_BMC (P < 0.001), Z_TB (P = 0.037), and Z_L1-4 (P < 0.001). In conclusion, almost half of peripubertal nonobese children were vitamin D deficient in winter. Adequate vitamin D status and adiposity contributed to good bone health in nonobese children. Considering the beneficial effects of adequate vitamin D status on bone health, the current DRI may be insufficient for preventing vitamin D deficiency in winter among Korean children.
Journal of Bone and Mineral Metabolism 01/2013; · 2.22 Impact Factor
[show abstract][hide abstract] ABSTRACT: Previous studies have shown that hematopoietic stem cell transplantation (HSCT) may result in growth impairment. The purpose of this study was to evaluate the growth during 5 yr after HSCT and to determine factors that influence final adult height (FAH). We retrospectively reviewed the medical records of acute myeloid leukemia (AML) patients who received HSCT. Among a total of 37 eligible patients, we selected 24 patients who began puberty at 5 yr after HSCT (Group 1) and 19 patients who reached FAH without relapse (Group 2). In Group 1, with younger age at HSCT, sex, steroid treatment, hypogonadism and hypothyroidism were not significantly associated with growth impairment 5 yr after HSCT. History of radiotherapy (RT) significantly impaired the 5 yr growth after HSCT. Chronic graft-versus-host disease (cGVHD) only temporarily impaired growth after HSCT. In Group 2, with younger age at HSCT, steroid treatment and hypogonadism did not significantly reduce FAH. History of RT significantly reduced FAH. Growth impairment after HSCT may occur in AML patients, but in patients without a history of RT, growth impairment seemed to be temporary and was mitigated by catch-up growth.
Journal of Korean medical science 01/2013; 28(1):106-13. · 0.84 Impact Factor
[show abstract][hide abstract] ABSTRACT: Trichomonas vaginalis is a flagellated protozoan parasite that causes human trichomoniasis. Although T. vaginalis itself can secrete lipid mediator leukotriene (LT) B(4) leading to neutrophil activation, information regarding the signaling mechanism involved in neutrophil activation induced by T. vaginalis-secreted LTB(4) is limited. We investigated whether LTB(4) contained in the T. vaginalis-derived secretory products (TvSP) is closely involved in interleukin (IL)-8 production in human neutrophils via LTB(4) receptors BLT1 or BLT2.
T. vaginalis produced more than 714 pg/ml of LTB(4) per 1 × 10(7) trichomonads. The ability of trichomonads to secrete LTB(4) was inhibited by treatment of trichomonads with the 5-lipo-oxygenease inhibitor AA861, but not the cyclo-oxygenease I inhibitor FR122047. When neutrophils were incubated with TvSP obtained from 1 × 10(7) trichomonads, IL-8 protein secretion was significantly increased compared to results for cells incubated with medium alone. The stimulatory effect of TvSP on IL-8 production was strongly inhibited by pretreatment of TvSP with lipase, although pretreatment with heat or proteinase K showed little inhibitory effect. Moreover, TvSP-induced IL-8 production was efficiently inhibited when trichomonads were pretreated with AA861 or when neutrophils were pretreated with antagonists for BLT1 or BLT2.
Our results suggest that LTB(4) receptors BLT1 and BLT2 are involved in IL-8 production in neutrophils induced by T. vaginalis.
Agents and Actions 01/2012; 61(2):97-102. · 1.59 Impact Factor
[show abstract][hide abstract] ABSTRACT: This study used positron emission tomography-computed tomography (PET-CT) to evaluate the effects of 4 anesthetic protocols on 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG) accumulation in the brains and hearts of miniature pigs (Sus scrofa domestica). The 18F-FDG standard uptake value was quantified by dividing the brain into 6 regions: cerebellum, brainstem, and frontal, parietal, temporal, and occipital lobes. Five (2 female and 3 male) clinically normal miniature pigs were premedicated with medetomidine (200 μg/kg IM) after which the following 4 anesthetic protocols were administered by using a crossover design: 1) propofol (4 mg/kg IV)-isoflurane inhalation; 2) propofol (4 mg/kg IV); 3) ketamine (5 mg/kg IV); 4) tiletamine-zolazepam (4.4 mg/kg IM). Compared with levels after other protocols, brain accumulation of 18F-FDG increased during propofol anesthesia but decreased with tiletamine-zolazepam. Relative to that due to other protocols, heart accumulation of 18F-FDG increased with propofol-isoflurane anesthesia but decreased with tiletamine-zolazepam. Comparing glucose accumulation in the brain and heart of miniature pigs by using PET-CT, we found that glucose accumulation varied according to the anesthetic protocol and between the 2 organs. These results can be used to evaluate how different anesthetic agents affect glucose metabolism in brain and heart of miniature pigs. Furthermore, these data should be considered when selecting an anesthetic agent for miniature pigs that will undergo PET-CT imaging with 18F-FDG.
Journal of the American Association for Laboratory Animal Science: JAALAS 01/2012; 51(2):246-52. · 1.15 Impact Factor
[show abstract][hide abstract] ABSTRACT: A 1-y-old male miniature pig housed in our laboratory facility was evaluated for weight loss and rough coat condition. CBC results revealed neutrophilia. Radiography of the thoracic area showed increased opacity throughout the thoracic cavity except for the right caudal lobe. ¹⁸F-labeled fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET-CT) revealed elevated standard uptake values in the area corresponding to the radiologic findings. Follow-up thoracic radiography taken 2 wk after FDG-PET-CT showed several interval changes, including markedly decreased opacity throughout the entire thoracic cavity. Necropsy revealed adhesions between the upper portion of the caudal lobe of the left lung and thoracic wall. ELISA for several closely related infectious species confirmed the presence of antibody to Actinobacillus pleuropneumoniae serovar V.
Comparative medicine 01/2012; 62(3):203-8. · 1.12 Impact Factor
[show abstract][hide abstract] ABSTRACT: Cell surface mucins configure the cell surface by presenting extended protein backbones that are heavily O-glycosylated. The glycopeptide structures establish physicochemical properties at the cell surface that enable and block the formation of biologically important molecular complexes. Some mucins, such as MUC1, associate with receptor tyrosine kinases and other cell surface receptors, and engage in signal transduction in order to communicate information regarding conditions at the cell surface to the nucleus. In that context, the MUC1 cytoplasmic tail (MUC1CT) receives phosphorylation signals from receptor tyrosine kinases and serine/threonine kinases, which enables its association with different signaling complexes that conduct these signals to the nucleus and perhaps other subcellular organelles. We have detected the MUC1CT at promoters of over 500 genes, in association with several different transcription factors, and have shown that promoter occupancy can vary under different growth factor conditions. However, the full biochemical nature of the nuclear forms of MUC1 and its function at these promoter regions remain undefined. I will present evidence that nuclear forms of the MUC1CT include extracellular and cytoplasmic tail domains. In addition, I will discuss evidence for a hypothesis that the MUC1CT possesses a novel catalytic function that enables remodeling of the transcription factor occupancy of promoters, and thereby engages in regulation of gene expression.
[show abstract][hide abstract] ABSTRACT: A single measurement of serum 17α-hydroxyprogesterone (17OHP) level can be unreliable because of its marked diurnal variation. We investigated the relationship of serum level of 17OHP with that of androstenedione (AD), which shows a smaller diurnal variation. And we tested whether the responses of these two hormones to low-dose ACTH stimulation are correlated in patients with 21-hydroxylase deficiency. Baseline serum 17OHP and AD levels were measured in 87 patients and a low-dose ACTH stimulation test was performed in 41 patients. The basal 17OHP level correlated positively with the basal AD level independently of sex, type of 21-hydroxylase deficiency, and the time of day of blood sampling (n = 87, R(2) = 0.75, P < 0.001). The area under the curve of 17OHP and AD correlated positively with their respective basal levels. The fold-change increase in 17OHP after ACTH injection correlated negatively with the basal 17OHP level, but that of AD did not correlate with the basal AD level. The random serum 17OHP level, used in the clinic, is a reliable guide and a low-dose ACTH stimulation test provides no extra benefit for assessing the treatment adequacy in patients with 21-hydroxylase deficiency.
Journal of Korean medical science 11/2011; 26(11):1454-60. · 0.84 Impact Factor
[show abstract][hide abstract] ABSTRACT: Diabetes is associated with atherogenic risk factors. Hypertension has a major influence on cardiovascular disease in diabetic patients. Ambulatory blood pressure monitoring (ABPM) is useful for identifying nocturnal hypertension. Carotid intima-media thickness (cIMT) is a good measure for identifying subclinical atherosclerosis. This study aimed to evaluate whether nocturnal hypertension affects atherosclerosis in children and adolescents with type 1 diabetes and to investigate the relationship between atherogenic risk factors and cIMT.
ABPM and cIMT were measured in 82 diabetic children and adolescents. We reviewed the hemoglobin A(1c) levels, 24-h urine microalbumin excretion, lipid profiles, and duration of diabetes. Nocturnal hypertension was defined as hypertension observed only at night.
Forty-three (52%) subjects were hypertensive, and 30 subjects were classified as having nocturnal hypertension. cIMT was higher in the nocturnal hypertensive group than in the normotensive group (0.44 ± 0.03 vs. 0.42 ± 0.04 mm, P = 0.026). Among children and adolescents with nonhypertensive blood pressure levels in clinic blood pressure monitoring, cIMT and daytime blood pressure were higher in the nocturnal hypertensive group. All ABPM parameters were significantly related to cIMT in multiple linear regression analysis.
This study showed significantly increased cIMT and daytime blood pressure in diabetic children and adolescents with nocturnal hypertension. ABPM may be a useful method for detecting the macrovascular complications of type 1 diabetes. Longitudinal studies are needed to find the causes of nocturnal hypertension and to evaluate the effect of nocturnal hypertension on atherosclerosis in type 1 diabetes.
Diabetes care 09/2011; 34(10):2180-5. · 7.74 Impact Factor
[show abstract][hide abstract] ABSTRACT: Trichomonas vaginalis is a flagellated lumen-dwelling extracellular protozoan parasite that causes human trichomoniasis via sexual intercourse. Human neutrophils play a crucial role in acute tissue inflammatory responses in T. vaginalis infection. In this study, we investigated the signaling mechanism of neutrophil responses when stimulated with T. vaginalis-derived secretory products (TvSP), which were collected from 1×10(7) live trichomonads. Incubation of human neutrophils isolated from peripheral blood with TvSP induced up-regulation of IL-8 protein secretion. In addition, stimulation with TvSP induced phosphorylation of NF-κB and CREB in neutrophils. Moreover, TvSP-induced IL-8 production was also significantly inhibited by pretreatment of neutrophils with iκB inhibitor or CREB inhibitor. These results suggest that transcription factors NF-κB and CREB are involved in IL-8 production in human neutrophils induced by stimulation with T. vaginalis infection.
The Korean Journal of Parasitology 09/2011; 49(3):291-4. · 0.88 Impact Factor
[show abstract][hide abstract] ABSTRACT: Tribromoethanol (2,2,2-tribromoethanol, TBE) is a popular injectable anesthetic agent used in mice in Korea. Our goal was to assess the risks associated with side effects (lesions) in the abdominal cavity, especially at high doses. To understand the underlying pathophysiological changes, we examined levels of cytokines through ELISA of abdominal lavage fluid and spleen collected from mice treated with low and high-dose TBE. ICR mice were anesthetized using one of the following protocols: a combination of TBE 200 mg/kg (1.25%) and xylazine 10 mg/kg; TBE 400 mg/kg (1.25%); and TBE 400 mg/kg (2.5%). Administration of high-dose TBE (400 mg/kg) increased the interleukin-1β and interleukin-6 levels in the peritoneal cavity over the short term (<1 day) compared with sham controls and low-dose TBE (200 mg/kg) groups. Cytokine expression in the low-dose TBE group was similar to the control group, whereas in the high-dose TBE group cytokine levels were higher in abdominal lavage fluid and spleen over the long term (10 days post-injection). We conclude that a combination of TBE 200 mg/kg (1.25%) and xylazine (10 mg/kg) is a safe and effective anesthetic for use in animals.
[show abstract][hide abstract] ABSTRACT: Trichomonas vaginalis is a protozoan parasite that causes acute tissue inflammation in vaginal trichomoniasis. In this study, we investigated the signaling mechanisms through which T. vaginalis-derived secretory products (TvSP) induce chemokine IL-8 production in human mast cells. Stimulation with TvSP induced up-regulation of IL-8 protein secretion in HMC-1 cells. In addition, TvSP induced phosphorylation of transcription factors NF-κB and CREB in HMC-1 cells. Pretreatment of TvSP with lipase, but not heat or proteinase K strongly abolished the stimulatory effect on IL-8 production. Moreover, TvSP-induced IL-8 production and phosphorylation of NF-κB or CREB were inhibited when HMC-1 cells were stimulated with modified TvSP collected from 5-lipooxygenase inhibitor-treated trichomonads. Indeed, T. vaginalis-secreted lipid mediator LTB(4) (700pg/ml) from 1×10(7) trichomonads. Furthermore, pretreatment of HMC-1 cells with antagonists for LTB(4) receptors BLT1 or BLT2 abolished the stimulatory effects of TvSP. Finally, TvSP-induced IL-8 production was inhibited by pretreatment with IκB or CREB inhibitors. These results suggest that T. vaginalis-derived secretory lipid mediator LTB(4) induces IL-8 production in mast cells via BLT-dependent activation of NF-κB and CREB.
Microbes and Infection 07/2011; 13(14-15):1211-20. · 2.92 Impact Factor
[show abstract][hide abstract] ABSTRACT: Entamoeba histolytica, which causes amebic colitis and occasional liver abscesses in humans, can induce host cell death through apoptosis and necrosis. Recently, we have demonstrated that E. histolytica can induce cell death in neutrophils via diphenyleneiodonium-sensitive NADPH oxidase (NOX)-derived reactive oxygen species (ROS). Although there are enzyme systems similar to the phagocyte NADPH oxidase system in many non-phagocytic cell types, the signaling role of NOX-derived ROS in cell death of human colon epithelial cells induced by E. histolytica remains obscure. Incubation of colon epithelial Caco2 tumor cell lines with amebic trophozoites resulted in intracellular ROS generation and cell death in a caspase-independent manner. Pretreatment with DPI, an inhibitor of NOX, strongly decreased E. histolytica-induced cell death in Caco2 cells. As identified by RT-PCR, NOX1 transcripts were highly expressed in Caco2 cells. siRNA-mediated suppression of NOX1 protein significantly inhibited E. histolytica-induced cell death and ROS response in Caco2 cells. These results suggest that NOX1 participates in the ROS-dependent cell death of colon epithelial cells induced by amebic adhesion during the early phase of intestinal amebiasis.
Microbes and Infection 06/2011; 13(12-13):1052-61. · 2.92 Impact Factor