Deoxycholate-induced colitis is markedly attenuated in Nos2 knockout mice in association with modulation of gene expression profiles

Autor: Eugene W. Gerner, Katerina Dvorak, Claire M. Payne, Harris Bernstein, Hana Holubec, Jose L. Padilla-Torres, David G. Besselsen, Natalia A. Ignatenko, Karen A. Blohm-Mangone, Carol Bernstein, Barbora Dvorakova, Harinder S. Garewal
Rok vydání: 2006
Předmět:
Zdroj: Digestive diseases and sciences. 52(3)
ISSN: 0163-2116
Popis: 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.
Databáze: OpenAIRE