| Ulcerative colitis (UC) , one of the two forms of inflammatory bowel disease (IBD) , is a chronic disorder that affects hundreds of thousands of patients who suffer from abdominal pain,diarrhea, gastrointestinal bleeding, malabsorp-tion, and weight loss. Despite recent advances in therapy, UC has a high morbidity and follows a course of exacerbations and remissions with approximately 25 - 50% of patients relapsing annually. The risk of colorectal cancer is also increased in UC. Hence, it is worthwhile to further investigate those factors that lead to UC.The pathogenesis of UC is still unclear, nevertheless, the immune contri -bution is acknowledged . UC is believed to be due to an abnormal mucosal T cell response to bacterial antigens from the gut lumen . Experimental data indicate that mucosal CD4+ T cells play an important role in the pathogenesis of UC. Based on the pattern of cytokine production, CD4 + T cells are generally distinguished into two different subtypes. T helper (Th) -1 response is characterized by secretion of interferon ( IFN) - gamma and tumor necrosis factor (TNF) - beta, and are associated with delayed - type hypersensitivity reactions, whereas Th2 response, which is characterized by secretion of the cyto-kines interleukin (IL) -4, IL-5, IL-9 and IL-13, is associated with humoral immune responses and allergy. The immune response is regulated by the concerted action of pro - and anti - inflammatory cytokines. The deregulation of this process causes immunological disorders, such as allergic and autoimmune diseases. Although the causes of UC currently are not fully understood, increas-ing evidence implicates cytokines are one of the key factors in the development of this disorder. The rationale for cytokine - targeted therapy has been refined significantly, and clinical studies have been initiated.Recent investigations have focused on transcription factors that regulate production and activation of cytokines, including the NF - kB , and signal transducers and activator of transcription ( STAT). Although their exact role in UC is still unknown, further studies may lead to identification of additional possible targets for therapeutic intervention that could improve management of the disease. The aim of our study was to characterize the expression of Thl and Th2 cytokines (IL-12, IFN -7, IL-4 and IL-13) and transcription fators STAT4 and STAT6 in UC.Thirty patients with UC and 30 controls who underwent colonoscopy were included. UC disease activity was determined using a clinical grading scale. Three patients were diagnosed as extensive disease,9 involved in left semicolon, and 18 patients limited in rectum. Biopsy specimens were snap - frozen in liquid nitrogen and stored at -70X1 until used.By using a tissue homogenizer, tissue samaples were homogenized , and total RNA were extracted. The expression of IL - 12, IFN -7, IL-4 and IL-13 were assessed by RT -PCR, using GAPDH as an internal standard. In colonic specimens, IL-12 was increased in moderately and severely active UC compared to controls ( P < 0.05). IFN - 7 were not upregulated and IL-4 and IL - 13 were decreased in UC.Protein was extracted from colon mucosa of UC to detect the expression of phosphorylated and non - phosphorylated STAT4 and STAT6. Electrophoretic mobility shift assay ( EMSA) was used to investigate the activation level of STAT6 in UC. Western blot analysis showed high levels of nuclear - localized STAT4 than controls ( P < 0. 05 ) , and as was phosphorylation of STAT6 and STAT6 DNA - binding activity. The levels of both cytoplasmic and nuclear - localized STAT6 were observed in all groups, and no statistically differences were found.JAK - STAT pathway is one major signaling pathway converting the cytokine signal into gene expression programs regulating the proliferation and differ-...
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