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

• Published in: Prostaglandins & other lipid mediators 2007-11, Vol.84 (3), p.98-107
• Main Authors: Lin, James A., Watanabe, Junji, Rozengurt, Nora, Narasimha, Ajay, Martin, Martin G., Wang, Jenny, Braun, Jonathan, Langenbach, Robert, Reddy, Srinivasa T.
• Format: Article
• Language: English
• Subjects: Animals; Bile acids; Cholates - adverse effects; COX-2; Crohn Disease - enzymology; Crohn Disease - etiology; Crohn Disease - mortality; Crohn Disease - pathology; Crohn's disease; Cyclooxygenase 1 - deficiency; Cyclooxygenase 1 - metabolism; Cyclooxygenase 2 - deficiency; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 - metabolism; Diet, Atherogenic; Dietary Fats - adverse effects; Female; Inflammation - chemically induced; Inflammatory bowel disease; Intestinal inflammation; Intestines - drug effects; Intestines - pathology; Male; Mice
• ISSN: 1098-8823
• DOI: 10.1016/j.prostaglandins.2007.04.004

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.