Expression And Role Of IL-38 In Inflammatory Bowel Diseases

Objective: To investigate the expression and cellular source of IL-38 in IBD,and to explore the role and mechanism of IL-38 in the development of IBD.Methods: Serum and colon specimens were collected from IBD patients and controls and DSS-induced colitis mouse model was established.IL-38 m RNA and protein expression in colonic tissues was detected by RT-q PCR and western blotting,its cell localization by immunohistochemistry and immunofluorescence,and its levels in serum by enzyme-linked immunosorbent assay.Intraperitoneal injection of IL-38 recombinant protein intervene DSS-induced colitis mice.The disease activity index,colon length and histopathological score were analyzed and the expression of inflammatory factors in colon tissues were determined by RT-q PCR.The RAW264.7 cells and bone marrow derived macrophage were further cultured in vitro,administering with recombinant IL-38 along with LPS stimulation.The inflammatory factors levels was detected by RTq PCR.Results: The expression of IL-38 in colon tissue was higher in CD and UC groups than that in control group,while there were no statistically significant differences in serum IL-38 levels.The IL-38 expression in colon and serum tissues of DSS and control group are similar to human results.Immunohistochemistry showed that IL-38 is mainly expressed in infiltrated cells of mucosa lamina propria.Immunofluorescence indicated that IL-38 is mainly derived from B cells in intestinal mucosa,as well as partly from macrophages in mice intestine.m IL-38 recombinant protein significantly alleviate body weight loss and colon length shortening,decreased disease activity index and pathological score in the DSS mice model.And the m RNA expression of inflammatory factors such as IL-1β,TNF-a and CCL-2 in colon tissues were also significantly downregulated.In vitro,m IL-38 inhibited LPS-induced IL-1β,IL-6,TNF-a,IL-10,CCL-2 and CCL-7 in RAW 264.7 cells and IL-1β,IL-6,TNF-a,and CCL-7 in bone marrow derived macrophage.Conclusion: IL-38 plays an anti-inflammatory role in the intestinal mucosal inflammation of IBD through inhibiting the secretion of inflammatory factors in macrophage,which is a potential therapic target for IBD.