Research On Effects Of IL-17 And Its Receptor Antibody In DSS Induced Experimental Colitis

[Objective]Inflammatory bowel disease is a chronic recurrent gastrointestinal inflammatory disease,composed of ulcerative colitis and Crohn's disease.In recent years,research show that Th17 cells play an important role in the pathogenesis of inflammatory bowel disease.The cytokine IL-17 secreted by Th17 cells is a potential therapeutic target.The most well-known forms of IL-17 are IL-17A and IL-17F;IL-17 receptor mainly has two subtypes of IL-17RA and IL-17RC.The objective of this study was to explore that whether neutralization of IL-17 and its receptor could weaken the effect of Th17 cells,and therefore delay or stop imflammatory bowel disease deterioration.[Materials and methods]Totally 84 C57BL/6J female mice were randomly divided into 7 groups.Control group drank water;the rest six groups of mice were fed with 4%DSS solution.DSS group only drank 4%DSS solution;DSS+NS group was intraperitoneal injected of saline;IL-17A+DSS group was intraperitoneal injected of IL-17A antibody;IL-17F+DSS group was intraperitoneal injected of IL-17F antibody;IL-17RA+DSS group was intraperitoneal injected of IL-17RA antibody;IL-17RC+DSS group was intraperitoneal injected of IL-17RC antibody.Intraperitoneal injection was on d2,d4,d6 in the process.Mice were killed on the 7th day.The serum content of IL-17 A,IL-17F,IL-17RA,IL-17RC were detected by ELISA.The expressions of IL-17RC,IL-17F,IL-17RA and IL-17A in the colon tissue were detected by immunohistochemistry and Western Blot method.The proportion of Th1,Tc,Th17 and Treg cells in the blood,spleen,mesenteric lymph nodes,intestinal lamina propria were detected by flow cytometry.[Results]1.During the 7 days treatment,compared with the Control group,the mice of DSS group,NS+DSS group,IL-17A+DSS group,IL-17RA+DSS group and IL-17RC+DSS group lost the weight and disease activity index increased significantly(p<0.05).The weight of mice in IL-17F+DSS group also slightly decreased,the disease activity index slightly increased,but not as much as the other DSS groups.All of the mice were killed at the end of 7 days treatment,finding that the colon length of DSS group,NS+DSS group,IL-17A+DSS group,IL-17RA+DSS group and IL-17RC+DSS group were shortened,and the histological score of colon tissue were increased(p<0.01)compared with the Control group.The mice colon length of IL-17F+DSS group was higher than the other DSS groups.In addition,the mice colon tissue histopathological score were lower than the other DSS groups.2.IL-17A,IL-17F,IL-17RA and IL-17RC in colon tissue were significantly increased in experimental colitis mice induced by DSS compared with the Control group(p<0.01).IL-17A,IL-17F,IL-17RA and IL-17RC in colon tissues were decreased respectively by IL-17A antibody,IL-17F antibody,IL-17RA antibody and IL-17RC antibody(p<0.05).IL-17F antibody can reduce the expression of IL-17A,IL-17F,IL-17RA and IL-17RC in colon tissues.3.Thl cells,Tc cells,Thl7 cells were increased in the blood,spleen,mesenteric lymph nodes and lamina propria of experimental colitis mice.Treg cells were decreased.IL-17F antibody can decreased Thl cells,Tc cells,Th17 cells,and increased Treg cells of experimental colitis mice.[Conclusions]1.In the blood and colon tissue of DSS induced experimental colitis mice,the expression of IL-17 and its receptor were significantly increased.And T cell subsets were unbalance in the whole body and local tissues.2.The expression of IL-17 and its receptor in peripheral blood and colon tissue can respectively be reduced by IL-17 and ite receptor antibodies.3.IL-17F antibody can alleviate the clinical symptoms of DSS induced experimental colitis mice and reduce the pathological scores.4.IL-17F antibody can reduce the expression of IL-17 and its receptors in blood and colon tissues of experimental colitis mice,reduce Thl7 cells,improve the imbalance of different subsets of T cells,and have a certain therapeutic effect.