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

Full 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.

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Author information

Author/s: Bernstein, Harris (H); Holubec, Hana (H); Bernstein, Carol (C); Ignatenko, Natalia A (NA); Gerner, Eugene (E); Dvorak, Katerina (K); Besselsen, David (D); Blohm-Mangone, Karen Ann (KA); Padilla-Torres, Jose (J); Dvorakova, Barbora (B); Garewal, Harinder (H); Payne, Claire M (CM);

Affiliation: Department of Cell Biology and Anatomy, College of Medicine, University of Arizona, Tucson, Arizona 85724-5044, USA. bernstein3(-atsign-)earthlink.net

Grants: 1P50CA95060-01 (Agency:NCI NIH HHS) ; 1R21CA111513-01A1 (Agency:NCI NIH HHS) ; CA23074 (Agency:NCI NIH HHS) ; CA72008 (Agency:NCI NIH HHS)

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Digestive diseases and sciences (Dig Dis Sci), published in United States. (Language: eng)

Reference: 2007-Mar; vol 52 (issue 3) : pp 628-42

Dates: Created 2007/04/10; Completed 2007/05/01; Revised 2007/12/03;

PMID: 17253130, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
Colitis - chemically induced; genetics; metabolism
DNA Damage
Deoxycholic Acid - adverse effects
Detergents - adverse effects
Dietary Supplements
Disease Models, Animal
Disease Progression
Gene Expression Profiling

Immunohistochemistry
Intestinal Mucosa - metabolism
Membrane Proteins - metabolism
Mice
Mice, Inbred Strains
Nitric Oxide Synthase - genetics; metabolism
Oligonucleotide Array Sequence Analysis
Oxidative Stress - genetics
Tight Junctions - physiology

Associated Chemicals: Detergents (0) ; Membrane Proteins (0) ; Deoxycholic Acid (83-44-3) ; Nitric Oxide Synthase (EC 1.14.13.39)

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