Reduced sensitivity of inducible nitric oxide synthase-deficient mice to chronic colitis

Background: Overproduction of nitric oxide by the inducible form of nitric oxide synthase (iNOS) has been implicated in colitis. Different authors hav e postulated both toxic and protective effects of nitric oxide (NO) in the pathophysiology of active inflammation. The objective of this study was to examine the role of iNOS in experimental chronic colitis using iNOS-deficie nt mice. Methods: For induction of colitis, mice received three cycles of 2 % of dextran sodium sulfate (DSS) (M.W. 40,000) treatment in drinking water . The degree of colonic inflammation, leukocyte infiltration, and the expre ssion of cell adhesion molecules were determined. INOS expression and nitro tyrosine were also determined by immunohistochemistry. Results; After DSS t reatment, a moderate colitis with marked cell infiltration was observed. In tense expression of iNOS was observed on infiltrating cells as well as on t he colonic mucosal epithelium in these animals. In the iNOS-deficient mice, tissue damage was significantly diminished. No iNOS or nitrotyrosine stain ing was found in iNOS-deficient mice. The number of infiltrating cells and the expression of mucosal adressin cell adhesion molecule-1 were significan tly attenuated in the DSS-treated colon of iNOS-deficient mice. Conclusion: Induction of iNOS seems to act as a critical toxic effector molecule in th e pathogenesis of chronic colonic inflammation. (C) 2001 Elsevier Science I nc.