Immunoregulation Of IL-33 On TNBS-induced Inflammatory Bowel Disease

Inflammatory bowel disease(IBD)is a kind of chronic nonspecific intestinal inflammatory diseases with unclear pathogeny,including Crohn's disease(CD)and ulcerative colitis(UC).Their main clinical manifestations are diarrhea,abdominal pain,intestinal obstruction and malignant tendency increasing morbidity of colorectal cancer.One of the most important immunological factors contributing to the IBD morbidity is Th1/Th2-type immune disorder and therefore the immune balance of intestinal mucosal becomes a key point in designing the new strategy aiming to prevention and cure of IBD.This issue aims at exploring the effect and potential mechanism of IL-33 on TNBS-induced IBD in mice to provide a new direction for treatment of clinical inflammatory bowel diseases.Objective To investigate the effect and immunological mechanism of IL-33 on TNBS-induced IBD in mice,as well as the therapeutic effect of alternative active macrophages(AAM)induced by IL-33 in IBD mice.Methods The model of mice induced by TNBS was established in this experiment.After treatment with IL-33,histopathological examination was used to observe the intestinal damage,immunofluorescence technique is responsible for detection of expression of macrophage-associated genes in colon tissues and real-time PCR was employed for detection of the expression of cytokines in these areas.The treatment effect of AAM transfusion in IBD mice is evaluated with many detection technologies like histopathological examination,immunofluorescence technology and RT-PCR.To detect the distribution of macrophages in colon tissues,F4/80+ GFP+ macrophages with or without IL-33 treatment were transfused and examined.Results IL-33 treatment obviously attenuated the inflammatory damage of IBD induced by TNBS in mice.The histopathologic injuries in IBD mice were lessened and TNF-alpha expression in damaged colon was reduced after IL-33 administration.Expression of marked genes Arg1 and YM1 were increased in AAM after treatment with IL-33.After transfusion of IL-33-treated macrophages,the pathologic damages in colon tissues were significantly decreased.F4/80+ GFP+ macrophages were mainly distributed in the lamina propria of colon tissues.Therefore,AAM obviously inhibited the development of IBD,reduced the histopathological injury and inflammatory cytokine TNF-? expression and alleviated the intestinal illness in a certain extent.Conclusion IL-33 treatment can obviously alleviate the progression of IBD induced by TNBS,and the potential mechanism of IL-33 may be related to induction of alternative activated macrophage polarization.