The Correlation Research On Interferon Regulatory Factor 5 And Ulcerative Colitis

Objective:Major types of Inflammatory bowel disease(IBD)include Crohn's disease(CD)and Ulcerative colitis(UC).Among them,the lesions of UC are limited to mucosa and submucosa of the large intestine,and the primary clinical symptoms of UC are abdominal pain and diarrhea with mucus or bloody purulent stool.Its etiology and pathogenesis are not yet clear,involving heredity,environment,microorganisms and immune factors,among which immune dysfunction is considered as an important factor.Interferon regulatory factor 5(IRF5)belongs to the family of transcription factors that modulate the activity of the immune system.It can regulate the expression of interleukin-6(IL-6),IL-12,tumor necrosis factor-?(TNF-?)and other inflammatory factors through the toll-like receptor pathway,and affect the inflammatory response of various immune cells.Thus it is involved in the occurrence and development of systemic lupus erythematosus,rheumatoid arthritis,Sjogren's syndrome and other autoimmune diseases.Studies have shown that inflammatory factors,such as IL-1?,IL-10,IL-13,IL-17 and TNF-?,play an important role in the pathogenesis of UC,and the increased expression level of IRF5 can increase the risk of UC while the specific mechanism of IRF5 in UC is still unclear.Therefore,this paper will first explore the difference of IRF5 expression level in the intestinal mucosal tissues of UC patients andhealthy people,then verify the effect of IRF5 gene systemic knockout on UC through UC animal model,finally discuss whether IRF5 influences the occurrence and development of UC by regulating the expression of inflammatory factors,so as to provide new ideas for the treatment of UC.Methods:1.The intestinal mucosal samples were collected of UC patients and normal healthy people,then the difference of IRF5 gene expression level between the two groups were compared by using immunohistochemistry staining scores.2.Whole-body IRF5 gene knockout heterozygous C57BL/6J mice were obtained,and their offspring genotypes were identified,so as to get wild-type mice as the control group and whole-body IRF5 gene knockout homozygous mice as the experimental group.3.Dextran sulfate sodium(DSS)was used to construct acute colitis model in mice.The colitis severity between the two groups was compared according to the stool characteristics,weight changes,Disease activity index(DAI),the gross view of the whole colon and pathological change.4.The colonic mucosal tissues of the two groups were obtained,then Quantitative real-time PCR was used to compare the expression level of inflammatory factors between the two groups.Results:1.According to the immunohistochemical staining score,the expression level of IRF5 gene in the intestinal mucosal tissues of UC patients was significantly higher than that of normal healthy people(4.48±3.06 vs 2.10±1.60,P<0.05).2.Symptoms of colitis,such as diarrhea,blood stools and weight loss,were lighter in the experimental group than in the control group,with lower DAI scores on day 6 and7(1.88±0.89 vs 2.79±0.64,P<0.05;1.29±0.84 vs 3.04±1.19,P<0.01)and less pronounced colonic shortening(6.50±0.23 vs 5.98±0.60,P<0.05).3.Compared with the control group,the experimental group showed higher levels of IL-1rn,IL-10,IL-13 and IL-17(P<0.05),lower levels of IL-1? and TNF(P<0.05),andno significant difference of IL-2 and IL-23(P>0.05).Conclusions:The expression level of IRF5 gene in the intestinal mucosal tissues of UC patients was higher than that of healthy people;and the whole-body IRF5 gene knockout homozygous mice showed less severe colitis symptoms and colon lesions than wild-type mice,indicating that downregulate the expression level of IRF5 has an alleviating effect on UC.Compared with wild-type mice,the expression level of anti-inflammatory cytokines was up-regulated and proinflammatory cytokines downregulated in the intestinal mucosal tissues of whole-body IRF5 gene knockout homozygous mice,indicating that IRF5 can affect the occurrence and development of UC by regulating the expression level of inflammatory cytokines in intestinal mucosal tissues.Selectively control the expression level of IRF5 is expected to be a new method for the treatment of UC.