Chaohui Zhu; Min Fan; Jianhua Zhu; Limin Cao; Xinyu Duan; Kai Wu
Abstract
Background: Vitamin D has anti-inflammatory efficacy against ulcerative colitis (UC), however, the mechanism is yet little understood. Objective: To investigate the immunomodulatory effects of vitamin D against the UC, and to explore the potential downstream mechanisms. Materials and methods: Serum vitamin ...
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Background: Vitamin D has anti-inflammatory efficacy against ulcerative colitis (UC), however, the mechanism is yet little understood. Objective: To investigate the immunomodulatory effects of vitamin D against the UC, and to explore the potential downstream mechanisms. Materials and methods: Serum vitamin D, Interferon-γ (IFN-γ) and Interleukin (IL)-17 levels of the patients with UC were quantified using enzyme-linked immunosorbent assay (ELISA). Long non-coding RNAs (lncRNAs) levels were determined by using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Peripheral blood mononuclear cells (PBMCs) were collected from healthy control subjects, stimulated with CD4+ T lymphocytes or helper T cells 17(Th17) differentiation conditions, and then exposed to calcitriol (vitamin D active form) or certain lentiviral treatment, followed by subsequent molecular level testing. For in vivo assay, mice were given 3% dextran sulfate sodium (DSS) to induce colitis. Results: Compared with the control group, vitamin D levels in the UCs were statistically lower, and there was a negative correlation between IL-17 and vitamin D in the UCs. The lncRNA OIP5-AS1 could decrease under calcitriol treatment in both CD4+ T cells and Th17 differentiation. The lncRNA OIP5-AS1 was a microRNA (miR)-26a-5p sponge and therefore modulated the Th17 cells and IL-6 expression. The lncRNA OIP5-AS1/miR-26a-5p/IL-6 axis mediated the regulation of calcitriol-induced Th17 differentiation. Calcitriol had therapeutic effects on the UC mouse models by regulating the lncRNA OIP5-AS1 related pathway. Conclusion: Vitamin D might have anti-inflammatory potential in the treatment of the UC.
Zeinab Rajabian; Farzad Kalani; Saeid Taghiloo; Mohsen Tehrani; Alireza Rafiei; Zahra Hosseini-khah; Vahid Hosseini; Abolghasem Ajami
Mojgan Mohammadi; Mohammad Javad Zahedi; Amin Reza Nikpoor; Mohammad Reza Baneshi; Mohammad Mahdi Hayatbakhsh
Volume 10, Issue 2 , June 2013, , Pages 83-92
Abstract
Background: Inflammatory bowel disease, an autoimmune disease, has two clinical manifestations including Crohn’s disease and ulcerative colitis (UC). IL-17 has been the target of intensive research in autoimmune diseases. The influence of Toll like receptor 4 (TLR-4) gene polymorphisms on IL-17 ...
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Background: Inflammatory bowel disease, an autoimmune disease, has two clinical manifestations including Crohn’s disease and ulcerative colitis (UC). IL-17 has been the target of intensive research in autoimmune diseases. The influence of Toll like receptor 4 (TLR-4) gene polymorphisms on IL-17 production has also been revealed in UC patients and tissue inflammation in mice. Objectives: To investigate the association between the TLR-4 gene polymorphisms, Asp299Gly and Thr399Ile and IL-17 serum levels with ulcerative colitis. Additionally, we aimed to study modulation effects of forenamed gene polymorphisms on IL-17 serum levels in UC patients and controls. Methods: A total of 256 healthy controls and 85 UC patients enrolled in our study. DNA was extracted and PCR-RFLP technique was employed to determine Asp299Gly and Thr399Ile polymorphisms in TLR-4 gene and IL-17 serum levels were measured by ELISA method. Results: There was no significant difference between the frequency of Asp299Gly A>G and Thr399Ile C>T in UC patients and controls. While IL-17 serum levels in UC patients were significantly higher than controls (p=0.003), no significant difference in IL-17 levels between different genotypes existed. Additionally, a significant inverse relationship was observed between hemoglobin level and IL-17 serum levels in UC patients (p=0.039). Conclusions: Increased IL-17 serum levels in our UC patients might be explained through the synergistic activity of IL-17/IL-23 axis and pro-inflammatory cytokines, causing severe clinical outcome in patients with IBD. The prolonged excretion of blood in stool driven by inflammatory process which causes iron metabolism disorder and anemia may elucidate the inverse correlation between hemoglobin and IL-17 serum levels in UC patients. Lack of association between the TLR-4 gene polymorphisms and UC in our study was consistent with the results from other Caucasian populations.
Mohammad Mahdi Hayatbakhsh; Mohammad Javad Zahedi; Mohsen Shafiepour; Amin Reza Nikpoor; Mojgan Mohammadi
Volume 9, Issue 2 , June 2012, , Pages 128-135
Abstract
Background: Crohn’s disease (CD) and ulcerative colitis (UC) are two major clinical presentations of inflammatory bowel disease (IBD). Many novel candidate genes have been found to be associated with increased risk for IBD. Recently IL-23 receptor gene is identified as an IBD associated gene in ...
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Background: Crohn’s disease (CD) and ulcerative colitis (UC) are two major clinical presentations of inflammatory bowel disease (IBD). Many novel candidate genes have been found to be associated with increased risk for IBD. Recently IL-23 receptor gene is identified as an IBD associated gene in genome-wide studies. Objective: To ascertain whether rs7517847 and rs1004819 SNPs in the IL-23 receptor gene are associated with UC in our population in Kerman, south east of Iran. Methods: A total of 85 patients with UC and 100 healthy controls enrolled in our study. Endoscopic procedure was performed for all patients to determine their disease severity. IL-23 receptor genotyping at positions rs7517847 and rs1004819 was done by PCR-RFLP technique. Results: The results of this study showed no association between the studied polymorphisms in the IL-23 receptor gene and UC in our population. However, we found a significant association between rs7517847 gene polymorphism in IL-23 receptor and two important clinical variables including blood in stool and bowel movements in UC patients. Conclusion: The rs7517847 gene polymorphism in IL-23R may be related to the presence of blood in stool and bowel movements in patients with UC. Further functional analysis with other known IL-23 receptor genotypes and/or other candidate genes is necessary to confirm any genetic association with UC in our population.
Mojgan Mohammadi; Mohammad Mahdi Hayatbakhsh; Mohammad Javad Zahedi; Mohammad Reza Jalalpour; Amin Pakgohar
Volume 8, Issue 3 , September 2011, , Pages 183-188
Abstract
Background: Patients with ulcerative colitis are at increased risk of inflammation. Interleukin 23 (IL-23) is a newly identified cytokine with increased expression in inflamed biopsies of colon mucosa in patients with Crohn's disease; however, there is inconsistent evidence on its role in ulcerative ...
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Background: Patients with ulcerative colitis are at increased risk of inflammation. Interleukin 23 (IL-23) is a newly identified cytokine with increased expression in inflamed biopsies of colon mucosa in patients with Crohn's disease; however, there is inconsistent evidence on its role in ulcerative colitis. Objective: We aimed to compare serum IL-23 level in patients with ulcerative colitis and normal controls and determine if serum IL-23 level increases with the severity of disease according to endoscopic findings. Methods: We quantified serum IL-23 levels from 60 patients with ulcerative colitis and 20 control individuals. All patients underwent endoscopic procedure to define the severity of disease. Patients were then stratified into 2 groups of "Mild" and "Severe" according to the endoscopic findings. Results: For comparison of serum IL-23 levels, Platelet count, ESR and CRP between the groups, Mann-Whitney U test and independent sample t test were employed, as appropriate. Pearson’s and spearman's correlation tests were employed to test the association of IL-23 with platelet count, CRP and ESR in patients. Our findings showed that serum IL-23 levels were increased in patients with ulcerative colitis compared to normal control. Moreover, patients in "Severe" group had higher serum IL-23 levels and ESR compared with those in "Mild" group. There was no significant sexual dimorphism in any of studied variables. Conclusion: We suggest that IL-23 plays an important role in the p