immunomodulatory effect 1, 25 [OH]2 D3 on TLR 2 and TLR4 expression on monocytes of patients with type II diabetes mellitus

Background: recent studies have shown the immunomodulatory effect of vitamin D3 through down-regulation of Toll-like receptor [TLR] expression in human monocytes. In this study, the effects of vitamin D treatment on TLR2 and TLR4 expression on monocytes derived from type 2 diabetes was investigated

Materials and Methods: to assess the influence of vitamin D3 on expression of TLR2 and TLR4 on monocytes from patients with type II diabetes, peripheral blood sample was taken of 30 patients. Peripheral blood mononuclear cells [PBMCs] were isolated by density gradient centrifuge and then monocytes were isolated from these cells with using the magnetic activated cell sorting [MACS]. To investigate the effect of vitamin D3 on the expression of TLR2 and TLR4, monocytes were cultured in the presence of vitamin D3 [10[-9] M] for 48 hours. Then the expression of TLR2 and TLR4 was determined by Real-time PCR

Results: we found that vitamin D3 suppresses the mRNA expression of TLR2 and TLR4 in patients with type II diabetes. TLR2 and TLR4 expression in the patients exposed to vitamin D3 were significantly decreased in comparison with patients who were not treated with vitamin D3

Conclusion: it can be concluded that vitamin D3 supplements may be further analyzed as a therapeutic option by reducing TLR2 and TLR4 expression in patients with type II diabetes

effect of vitamin A supplementation on disease progression, cytokine levels and gene expression in multiple sclerotic patients: study protocol for a randomized controlled trial

Multiple Sclerosis [MS] is a chronic inflammatory disease that leads to degeneration of the brain and spinal tissue. Imbalances of CD4+ T cells including Thelper1 [Th1]/Thelper2 [Th2] and Thelper17 [Th17]/Tregulatory [Treg], their secreted cytokines and gene expressions, are important aspects of in immunopathogenesis of MS. Vitamin A and its metabolites can regulate the immune system and appears to be effective in preventing progression of the autoimmune disease such as MS. Disease progression was evaluated By Magnetic Resonance Imaging [MRI], Expanded Disability States Scale [EDSS] and Multiple Sclerosis Functional Composite [MSFC] tests. Cytokine levels were measured using ELISA kits and gene expression was quantified by Real time PCR [RT-PCR] system. According to the difference between the epidemiological and clinical data on the relationship between vitamin A and immune system regulation, this study of the first time assesses Immune function as well as gene expression and progression of the disease following administration of vitamin A supplement

[Prevalence of ERCC1 overexpression and its relation with response to Cisplatin-based chemoradiation in cervical cancer]

Although current treatment options for cervical cancer rely on platinum-based chemoradiotherapy, individualized approaches to therapy may improve response or reduce unnecessary toxicity. Over expression of Excision repair cross-complementing 1 [ERCC1] has been associated with Cisplatin resistance in some tumors. We hypothesized that ERCC1 over expression is related to treatment response. 32 patients with cervical cancer were enrolled. Malignant tissue was isolated from pretreatment biopsies, and quantitative real-time reverse transcriptase polymerase chain reaction assays were performed to determine ERCC1 expression. Patients were divided to ERCC1 positive and ERCC1 negative. Response to chemoradiotherapy was evaluated and compared among the two groups. The mean age of participants was 56.6 +/- 12 years. Objective response was obtained in 24 patients [75%]. ERCC1 was 2.8 times higher in patients who did not respond to treatment compared with the responders [OR: 2.8]. Assessment of ERCC1 expression in tumoral tissue is possible in the clinical setting and predicts response to chemoradiotherapy. Further studies are necessary for final judgment

Effect of all-trans retinoic acid [ATRA] on viability, proliferation, activation and lineage-specific transcription factors of CD4+ T cells

All-trans retinoic acid [ATRA], as an active metabolite of vitamin A, has been shown to affect immune cells. This study was performed to evaluate the effect of ATRA on viability, proliferation, activation and lineage-specific transcription factors of CD4+ T cells. CD4+ T cells were separated from heparinized blood of healthy donors and were cultured in conditions, some with, some without ATRA. Viability was assessed by PI flowcytometry and proliferation was measured by MTT assay. CD69 expression was determined by flowcytometry as a measure of cell activation. Lineage-specific transcription factors [FOXP3, RORgammat and T-bet] were examined by intracellular staining and flowcytometry. High doses of ATRA [0.1-1 mM] caused extensive cell death in both PBMCs and CD4+ T cells. Doses of ATRA equal to or lower than 10 microM did not adversely affect cell viability and proliferation in comparison to culture medium without ATRA. Doses of ATRA between 10 microM and InM significantly increased cell activation when compared to culture medium without ATRA. ATRA could increase FOXP3+ and also FOXP3+RORgammat+ T cells while it decreased RORgammat+ and T-bet+ T cells. This study showed that doses of ATRA up to 10 microM are safe when using with CD4+ T cells in terms of cell viability, proliferation and activation. We could also show that ATRA diverts the human immune response in neutral conditions [without adding polarizing cytokines] by increasing FOXP3+ cells and decreasing RORgammat+ cells. ATRA could be regarded as a potential therapy in inflammatory conditions and autoimmunities

Decreased T cell response to mitogen and increased anti-cytoplasmic antibody in drug-free schizophrenic patients

Apart from genetic and environmental factors, activation of autoreactive mechanisms has been proposed to play a role in the pathogenesis of schizophrenia. In recent years, considerable work has been carried out to understand the role and contribution of the immune system in this disease. To investigate the T cell response to phytohaemagglutinin [PHA] and determine the serum levels of anti-nuclear antibody [ANA], anti-cytoplasmic antibody [ACA], and circulating immune complexes [CIC] in schizophrenic patients. A total of 30 drug-free schizophrenic patients and 42 healthy controls were enrolled in this study. T cell proliferation in response to PHA was measured using Methyl Thiazol Tetrazolium test. ANA and ACA were measured by indirect immunofluorescence. CIC concentration was determined using poly ethylene glycol precipitation assay. Mean PHA response was 1.96 +/- 0.83 in patients and 3.72 +/- 1.39 in healthy controls [p < 0.001]. ANA and CIC concentrations were not significantly different between two groups. In addition, ACA was detected only in patients. Increased production of ACA together with lower T cell response to mitogens in our patients provides evidence for the involvement of autoimmune mechanisms in the pathogenesis of schizophrenia

Increased expression of trail and its receptors on peripheral T-cells in type 1 diabetic patients

Type-I diabetes is an autoimmune inflammatory disease in which pancreatic beta-cells are selectively destroyed by infiltrating cells. TNF-related apoptosis-inducing ligand [TRAIL] is a type-II membrane protein of the TNF superfamily which is expressed in different tissues, including pancreas and lymphocytes. In humans, TRAIL interacts with four membrane receptors. TRAIL-R1 and TRAIL-R2 have cytoplasmic death domains, and can activate both caspases and NF?B pathways. The other two receptors, TRAIL-R3 and TRAIL-R4, are decoy receptors not capable of activating caspase cascade but may activate NF-?B and block apoptosis. As human beta cells are sensitive to TRAIL induced apoptosis, signaling via these molecules is considered to be a probable way of beta cell destruction. These molecules also are important in suppression of autorective T cells and immunoregulation. To explore the importance of TRAIL and its receptors at pathogenesis of type-I diabetes, we compared expression of these molecules on T-cells of diabetic patients and healthy controls. In this study, expression of TRAIL and its receptors at protein and mRNA levels were studied in freshly isolated peripheral T cells of 55 type I diabetic patients and 50 healthy individuals by flowcytometry, western blot and RT-PCR. We found that expression of TRAIL and its receptors in peripheral T-cells at both protein and mRNA levels are significantly increased in patients [except for TRAIL-R2 mRNA which was slightly higher in controls] but increase in TRAIL, TRAILR3 [2.7% vs. >0.5%] and TRAIL-R4 [2.6% vs. >0.5%] is more considerable. sTRAIL in sera of patients was significantly lower than in controls [p=0.01]. Our results explain resistance of autoreactive T-cells to immunoregulatory mechanisms. Besides, increased expression of TRAIL in autoreactive T-cells may play an important role in betacell destruction. Lower level of sTRAIL in diabetic patients may be a reason for hyperactivation of autoreactive T-cells

Increased natural killer cell activity in schizophrenic patients

Schizophrenia has been associated with altered immunity. Different studies regarding natural killer cell activity [NKA] in schizophrenic patients have shown inconsistent results. To evaluate NK cell activity in schizophrenic patients in comparison with healthy control individuals. 30 medication-free schizophrenic patients and 41 healthy sex, age and smoking status matched individuals were included in this study. NK cell activity of case and control subjects was measured by Methyl-Thiazol-Tetrazolium [MTT] test. Statistical analysis of the data was done using SPSS 11.5 software. NK activity of patients and normal subjects had a mean of 36.94 +/- 26.15 [Mean +/- SD] and 22.31 +/- 17.92, respectively. A significant increase in NK activity in schizophrenic patients compared to controls [P = 0.011]. Among patients, NK activity of smokers was significantly lower than that of non-smokers [P = 0.02]. Other demographic factors didn't show any influence on NK activity. The higher activity of NK cells in the schizophrenic patients as compared with the control population could explain the low incidence of cancer in these patients. Decreasing the effect of smoking on NK activity in the patients could be one of the responsible factors for the inconsistency in the results of different studies