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.