P075 Adaptive defensive response is critical to determine dextran sulphate sodium-induced colitis

Dextran sulphate sodium (DSS)-induced colitis in mice is one of the most frequent and useful animal model in the study of inflammatory bowel disease, of which pathogenesis are immune derangement and mucosal damages. Curiously, colitis usually developed after 4–5 days of DSS administration in spite of its toxicity. We hypothesised host defense system might delay the presentation of colitis after DSS administration. We measured the serial expressions of either inflammatory mediators and signalling or host defense Phase 2 enzyme with signalling in wild-type mice administered with DSS, COX-2 KO, and Nrf2 KO mice. Dextran sulphate sodium (DSS)-induced colitis in mice is one of the most frequent and useful animal model in the study of inflammatory bowel disease, of which pathogenesis are immune derangement and mucosal damages. Curiously, colitis usually developed after 4–5 days of DSS administration in spite of its toxicity. We hypothesised host defense system might delay the presentation of colitis after DSS administration. In accordance with emergence of colitis, COX-2 expressions correlated with degree of colitis as much as NF-kB activation (p < 0.01). When traced the expressions of host defense proteins such as HO-1, NQO-1, γ-GCS, HO-1 expressions with Nrf2 induction were also significantly correlated with COX-2 expressions. When colitis was induced in COX KO mice with DSS administration, significantly lowered damages were noted, in which HO-1 expressions were also significantly decreased compared with WT littermates (p < 0.001). On the other hand, when colitis was induced in Nrf2 KO mice, significantly higher degree of colitis was noted, in which COX-2, HO-1, and γ-GCS were significantly increased compared with WT littermates (p < 0.01). Host defense system can determine the degree of colitis, by which medications enhancing defense systems might be prerequisite in the treatment of IBD.