Deoxycholate-induced colitis is markedly attenuated in Nos2 knockout mice in association with modulation of gene expression profiles.
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.
Bernstein
Harris
H
Department of Cell Biology and Anatomy, College of Medicine, University of Arizona, Tucson, Arizona 85724-5044, USA. bernstein3@earthlink.net
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
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
D003902:Detergents; D008565:Membrane Proteins; D003840:Deoxycholic Acid; D019001:Nitric Oxide Synthase