title: Deoxycholate-induced colitis is markedly attenuated in Nos2 knockout mice in association with modulation of gene expression profiles.
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.
authors.affiliation: Department of Cell Biology and Anatomy, College of Medicine, University of Arizona, Tucson, Arizona 85724-5044, USA. bernstein3@earthlink.net
authors.forename: Harris
authors.initials: H
authors.lastname: Bernstein
authors.forename: Hana
authors.initials: H
authors.lastname: Holubec
authors.forename: Carol
authors.initials: C
authors.lastname: Bernstein
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Ignatenko
authors.forename: Eugene
authors.initials: E
authors.lastname: Gerner
authors.forename: Katerina
authors.initials: K
authors.lastname: Dvorak
authors.forename: David
authors.initials: D
authors.lastname: Besselsen
authors.forename: Karen Ann
authors.initials: KA
authors.lastname: Blohm-Mangone
authors.forename: Jose
authors.initials: J
authors.lastname: Padilla-Torres
authors.forename: Barbora
authors.initials: B
authors.lastname: Dvorakova
authors.forename: Harinder
authors.initials: H
authors.lastname: Garewal
authors.forename: Claire M
authors.initials: CM
authors.lastname: Payne
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D004249:DNA Damage; D003840:Deoxycholic Acid / Q000009:adverse effects; D003902:Detergents / Q000009:adverse effects*; D019587:Dietary Supplements; D004195:Disease Models, Animal; D018450:Disease Progression; D020869:Gene Expression Profiling; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000235:genetics; D019108:Tight Junctions / Q000502:physiology
chemical_list: D003902:Detergents; D008565:Membrane Proteins; D003840:Deoxycholic Acid; D019001:Nitric Oxide Synthase