We investigated differences in the pathogenesis of dextran sulfate sodium (DSS)-induced colitis between two inbred rat strains, Wistar King A Hokkaido (WKAH) and Dark Agouti (DA) rats, to determine the intrinsic factors responsible for the development of colitis. DSS exposure exacerbated the clinical symptoms such as body weight loss, stool consistency and rectal bleeding in DA rats rather than that in WKAH rats. Additionally, the average survival was shorter in DA rats than in WKAH rats. The expression levels of tumor necrosis factor-α, interleukin (IL)-12 p35 and IL-23 p19 increased prominently in the DA rats that were administered DSS, accompanied by severe infiltration of leukocytes into the colon. We also found that colonic permeability was greater in the DA rats than in the WKAH rats. In Ussing chambers, exposure of the isolated colon tissue to DSS enhanced the colonic permeability of both strains. Immunoblot analysis revealed that the expression levels of tight junction (TJ) proteins were modulated during DSS administration. Higher expression levels of claudin-4 and junctional adhesion molecule-A proteins were observed in DA rats than in WKAH rats, even in intact conditions. These results indicated that the expression pattern of TJ proteins determines the colonic permeability of the rats. In conclusion, the intrinsic colonic permeability is one of critical factors responsible for the susceptibility of rats to colitis.

We investigated the differences in the pathogenesis of dextran sulfate sodium (DSS)‐induced colitis between two inbred rat strains, WKAH and DA rats, to determine an intrinsic factor responsible for the development of colitis. The body weight reduction, stool consistency, and rectal bleeding were daily evaluated during DSS treatment period. The clinical symptoms in DA rats were significantly severer than that in WKAH rats. In an early phase of DSS treatment period, we measured the expressions of cytokine mRNA and tight junction (TJ) proteins in the colonic mucosae. DSS treatment increased prominently the mRNA expression levels of TNF‐α, IL‐12 p35, and IL‐23 p19 in the DA rat. A colonic permeability was greater in the DA rats than in the WKAH rat. Higher expression of claudin‐4 and Junctional adhesion molecule (JAM)‐A proteins were observed in the DA rats than that in the WKAH rats without DSS conditions. The different expression pattern of TJ proteins probably determines the colonic permeability of rats. However, DSS treatment enhanced TNF‐α production in mesenteric leukocytes isolated from the WKAH rats rather than that from DA rats, suggesting that the response of immune cells to DSS in the DA rats was weaker than that of the WKAH rats. In conclusion, the intrinsic colonic permeability is one of critical factors responsible for the susceptibility to colitis.