ROLE OF RAGE DURING INTESTINAL INFLAMMATION AND ITS THERAPEUTIC POTENTIAL IN IBD

Objectives: The global aim of our study was to address the role of AGE and RAGE in Inflammatory Bowel Diseases. Methods: 1/ Intestinal and colonic inflammation were induced in WT and RAGE-/- mice. 2/ WT Mice were orally administered with CML-BSA or control BSA for 30 days, then intestinal and colonic inflammation were induced. In both experiments, severity of inflammation was evaluated using macroscopic, histologic and molecular parameters in the small intestine and colon. Main Results: A significant decrease in ulcerations number and area and IL1beta mRNA levels were observed in the duodenum, jejunum and ileum of RAGE-/- mice induced for intestinal inflammation. A significant decrease of clinical and macroscopic parameters, myeloperoxidase (MPO) activity and IL1beta and iNOS mRNA expression was observed in RAGE-/- mice challenged for colonic inflammation. Chronic BSA-CML administration to mice worsened enteritis, as evidenced by a significant increase in ulcerations number and area in the duodenum, jejunum and ileum and MPO activity and oxidative stress in the ileum. Conclusions: RAGE signaling pathway is implicated in intestinal and colonic inflammation in mice. BSA-CML might be a dietary factor involved in the pathophysiology of intestinal diseases.