Studies on the role of ALOX15 and its products in murine experimental colitis.

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Preliminary unpublished data from our laboratories show that mice with a systemic knockout of the alox15 gene (12/15-lipoxygenase deficient mice) are protected from DSS-induced colitis.The main objective of the proposed project are: (1) to understand the role of alox15 in the pathogenesis of DSS-induced colitis in mice and to validate these findings on other murine colitis models, and (2) to characterize in a cell culture model the molecular mechanisms of the effect of 12/15-lipoxygenase activity and its metabolites on the function of intestinal cells.Given that the preliminary data showing a pro-inflammatory effect of ALOX15 colitis can be confirmed, and the underlying molecular pathomechanisms be identified, selective inhibitors of ALOX15 could be potential drugs for the treatment of inflammatory bowel diseases.