Dual roles of IL-18 in colitis through regulation of the function and quantity of goblet cells.

Abstract

The main aim of the present study was to investigate the dual roles and mechanism of interleukin (IL)-18 in dextran sulfate sodium (DSS)-induced colitis. Firstly, meta-analysis was used to explore whether the levels of IL-18 were different in patients with colon cancer or inflammatory bowel disease. The results demonstrated that IL-18 (rs187238, -137G/C) increased the incidence rate of colon cancer in patients, while IL-18 (rs187238, -137G/C) decreased the incidence rate of ulcerative colitis or Crohn's disease in patients. Therefore, IL-18 (rs187238, -137G/C) may have a dual function in colitis. Next, the functional role of IL-18 in colitis was further investigated, by use of a DSS-induced colitis mouse model. Pre-treatment of the mice with IL-18 increased body weight, augmented colon length, reduced inflammatory infiltration, promoted mucin (Muc)-2 expression, increased the function and quantity of goblet cells and increased the mRNA levels of resistin-like molecule (RELM) β and trefoil factor family (TFF) 3 in mice with DSS-induced colitis, through the IL-22/STAT3 pathway. By contrast, treatment with IL-18 at later stages of the disease reduced body weight, decreased colon length, enhanced inflammatory infiltration and reduced Muc-2 expression, decreased the function and quantity of goblet cells and inhibited the mRNA levels of RELMβ and TFF3 in mice with DSS-induced colitis. In conclusion, IL-18 served a dual function in colitis by regulating the function of goblet cells. The anti-inflammatory effects of IL-18 were observed in the early stage of colitis-induced inflammation, while the pro-inflammatory effects were observed in the later stages of the disease.