The Mechanism And Effect Of Rapamycin On Trinitrobenzene Sulfonic Acid-induced Inflammatory Bowel Disease In Mice

Inflammatory bowel disease (IBD) is a non-specific intestinal chronic inflammatorydiseases，divided into Crohn’s disease (CD) and ulcerative colitis (UC)， can lead todiarrhea, abdominal pain, and even induced colon cancer risk. Immune factors play animportant role in the pathogenesis of the disease. Overreaction of T cell immune responseand disorder of immune homeostasis are considered important factors in causinginflammatory bowel disease. In this article, we observed the effect of rapamycin inTNBS-induced IBD, and explored the potential mechanism of rapamycin including theproportion of CD4+T cell subsets, the expression of cytokines and inflammatory mediatorsand other aspects. Additionally, we found that rapamycin can induce alternative activationof macrophages (AAM) differentiation during this experiment. We study the effect ofalternative activation of macrophages adoptive therapy for IBD, and in order to providenew ideas and directions for clinical treatment of IBD.Objective:We observed treatment effect of rapamycin on TNBS-induced IBD in mice, anddetected the immunological mechanism. We also do research on the effect of alternativeactivation of macrophages adoptive therapy for IBD, and in order to provide new ideas anddirections for clinical treatmentMethods:The percentage of T cells subsets and cytokine expression were detected in mice withTNBS colitis treated with/without rapamycin. The effect of AAM induced by rapamycin in vivo and in vitro were investigated either. Finally, peritoneal AAM induced in vivo byinjecting mice with rapamycin were transferred into mice with TNBS colitis.Results:Rapamycin can reduced the severity of TNBS colitis via regulate differentiation of Tcells. Inflammatory cytokines like IL-4, IL-6and TNF-α were inhibited while theexpression of TGF-β was increased. Rapamycin enhanced the expression of AAM-relatedmarkers in F4/80+cells in vivo and in vitro. Peritoneal F4/80+cells isolated fromRAPA-treated mice reduced the severity of TNBS colitis when injected intraperitoneally torecipient mice, and reduced the differentiation of T helper cells and promote thedifferentiation of regulatory T cells. The expression of inflammation-associated cytokineswas suppressed by AAM and that of TGF-β was enhanced in TNBS-induced IBD mice.Conclusions:The rapamycin-mediated anticolitic effect is associated with up-regulating thedifferentiation of Treg and induction of AAM, a subset of macrophages withanti-inflammatory properties.