Erschienen in:
01.03.2007 | Original Paper
Deoxycholate-Induced Colitis is Markedly Attenuated in Nos2 Knockout Mice in Association with Modulation of Gene Expression Profiles
verfasst von:
Harris Bernstein, Hana Holubec, Carol Bernstein, Natalia A. Ignatenko, Eugene Gerner, Katerina Dvorak, David Besselsen, Karen Ann Blohm-Mangone, Jose Padilla-Torres, Barbora Dvorakova, Harinder Garewal, Claire M. Payne
Erschienen in:
Digestive Diseases and Sciences
|
Ausgabe 3/2007
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Abstract
Nos2 knockout mice were compared to wild-type mice for susceptibility to colitis in response to a diet supplemented with deoxycholate, a bile acid increased in the colon of individuals on a high-fat diet. Wild-type mice fed a fat-related diet, supplemented with 0.2% DOC, develop colonic inflammation associated with increases in nitrosative stress, proliferation, oxidative DNA/RNA damage, and angiogenesis, as well as altered expression of numerous genes. However, Nos2 knockout mice fed a diet supplemented with deoxycholate were resistant to these alterations. In particular, 35 genes were identified whose expression was significantly altered at the mRNA level in deoxycholate-fed Nos2(+/+) mice but not in deoxycholate-fed Nos2(–/–) mice. Some of these alterations in NOS2-dependent gene expression correspond to those reported in human inflammatory bowel disease. Overall, our results indicate that NOS2 expression is necessary for the development of deoxycholate-induced colitis in mice, a unique dietary-related model of colitis.