Atherogenic diet causes lethal ileo-ceco-colitis in cyclooxygenase-2 deficient mice

Cyclooxygenases (COX) regulate a variety of inflammatory diseases, including inflammatory bowel disease (IBD). While the pathological effects of COX-1 inhibition by NSAIDs on intestinal ulceration are well established, the role of COX-2 on intestinal inflammation remains under investigation. In this paper, we report a protective role for COX-2 against diet-mediated intestinal inflammation in mice. COX-2(-/-) mice fed an atherogenic diet or diet containing cholate, but not chow or fat alone, had a high mortality whereas COX-1(-/-) mice and wild-type mice were unaffected by the dietary changes. Histological analysis identified the cause of death in COX-2(-/-) mice due to severe intestinal inflammation that was surprisingly limited to the ileo-ceco-colic junction. COX-2 expression is induced in the cecum of wild-type mice fed an atherogenic diet. Our findings show that COX-2 plays an anti-inflammatory role at the ileo-ceco-colic junction in mice, and the pathology of diet-mediated intestinal inflammation in COX-2(-/-) mice offers an excellent model system to elucidate the molecular mechanisms of intestinal inflammation.