title: Role of inducible nitric oxide synthase in the regulation of VCAM-1 expression in gut inflammation.
abstract: The objectives of this study were to assess the role of the inducible isoform of nitric oxide synthase (iNOS) on vascular cell adhesion molecule 1 (VCAM-1) expression in vivo in an acute model of inflammation induced in iNOS-deficient (iNOS-/-) mice and compare these data to those obtained by pharmacological inhibition of iNOS in a CD4+ T lymphocyte-dependent model of chronic colitis. VCAM-1 expression was quantified in vivo using the dual radiolabel monoclonal antibody technique. We found that intraperitoneal injection of 10 microg/kg tumor necrosis factor-alpha (TNF-alpha) enhanced VCAM-1 expression by approximately twofold in the colon, cecum, and stomach but not small intestine in iNOS-/- mice compared with TNF-alpha-injected wild-type mice. Injection of wild-type mice with 25 microg/kg TNF-alpha further enhanced VCAM-1 expression by approximately twofold compared with wild-type mice injected with 10 microg/kg TNF-alpha; however, VCAM-1 expression was not further enhanced in any gastrointestinal organ system in iNOS-/- mice. In a second series of experiments, we found that continuous inhibition of iNOS using oral administration of NG-iminoethyl-L-lysine did not alter the enhanced levels of VCAM-1 expression in the colon nor did it alter the severity of colonic inflammation in SCID mice reconstituted with CD4+, CD45RB(high) T cells. We conclude that iNOS may regulate VCAM-1 expression in acute inflammation; however, this effect is modest and tissue specific and occurs only when VCAM-1 expression is submaximal. iNOS does not appear to modulate VCAM-1 expression in an immune model of chronic colitis.
authors.affiliation: Department of Molecular and Cellular Physiology, Louisiana State University Medical Center, Shreveport, Louisiana 71130, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kawachi
authors.forename: A
authors.initials: A
authors.lastname: Cockrell
authors.forename: F S
authors.initials: FS
authors.lastname: Laroux
authors.forename: L
authors.initials: L
authors.lastname: Gray
authors.forename: D N
authors.initials: DN
authors.lastname: Granger
authors.forename: H C
authors.initials: HC
authors.lastname: van der Heyde
authors.forename: M B
authors.initials: MB
authors.lastname: Grisham
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D002908:Chronic Disease; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D017493:Leukocyte Common Antigens / Q000032:analysis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D016513:Mice, SCID; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D017493:Leukocyte Common Antigens