IL-18 aggravated ulcerative colitis by inhibiting the development of goblet cells through KLF4 in mice

Abstract:

Objective：To observe the role and mechanism of interleukin-18（IL-18） in intestinal mucosal barrier in dextran sulfate sodium（DSS）-induced colitis in mice. Methods：Mice were randomly divided into three groups：control group，DSS group（fed with DSS continually for 7 days） and DSS+IL-18 group（fed with DSS continually for 7 days and given injections of IL-18）. The weight of the mice were measured every day. Seven days later，colon tissues were collected and histology analysis were performed；goblet cell amount in histological sections was measured；the expression of the IL-18 and Kruppel-like factors-4（KLF4） were analyzed by Western bolt. Results：Compared with control group，the mice weight of DSS group loss significantly（P=0.000）. Damaged intestinal mucosa，reduced villous height，and deterioration of tissue integrity was corroborated by histological examination of distal colon sections performed on DSS group. The number of goblet cell in histological sections showed a dramatic decrease in DSS-treated mice compared to control group（control group：43.600±7.092，DSS group：16.000±6.205，P=0.000）. The protein expression of IL-18 in DSS group increased（control group：0.444±0.073；DSS group：0.649±0.062；P=0.006），but the KLF4 expression decreased（control group：0.777±0.081；control group：0.934±0.053；P=0.018）. Compared with DSS group，the weight of mice in DSS+IL-18 group decreased more significantly（P=0.000），the intestinal mucosa was damaged more severely，the number of goblet cell reduced dramatically（DSS+IL-18 group：3.200±2.863，P=0.004），the expression of IL-18 increased obviously（0.903±0.037，P=0.002），and the expression of KLF4 decreased（0.469±0.037，P=0.001）. Conclusion：IL-18 may aggravate ulcerative colitis by inhibiting the development of goblet cells through KLF4 expression reduction in mice.