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.
Lin
James A
JA
Department of Pediatrics, University of California Los Angeles, Los Angeles, CA 90095-1679, USA.
Watanabe
Junji
J
Rozengurt
Nora
N
Narasimha
Ajay
A
Martin
Martin G
MG
Wang
Jenny
J
Braun
Jonathan
J
Langenbach
Robert
R
Reddy
Srinivasa T
ST
D000818:Animals; D020355:Cholates / Q000009:adverse effects; D003424:Crohn Disease / Q000201:enzymology* / Q000209:etiology* / Q000401:mortality / Q000473:pathology; D051545:Cyclooxygenase 1 / Q000172:deficiency / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D004036:Diet, Atherogenic; D004041:Dietary Fats / Q000009:adverse effects; D005260:Female; D007249:Inflammation / Q000139:chemically induced; D007422:Intestines / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice
D020355:Cholates; D004041:Dietary Fats; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2