Role of inducible nitric oxide synthase in the regulation of VCAM-1 expression in gut inflammation
Kawachi, S.; Cockrell, A.; Laroux, F.S.; Gray, L.; Granger, D.N.; van der Heyde, H.C.; Grisham, M.B.
American Journal of Physiology 277(3): G572-G576
1999
ISSN/ISBN: 0002-9513 PMID: 10484382 Document Number: 508567
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 mg/kg tumor necrosis factor-a (TNF-a) enhanced VCAM-1 expression by approximately twofold in the colon, cecum, and stomach but not small intestine in iNOS-/- mice compared with TNF-a-injected wild-type mice. Injection of wild-type mice with 25 mg/kg TNF-a further enhanced VCAM-1 expression by approximately twofold compared with wild-type mice injected with 10 mg/kg TNF-a; 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+, CD45RBhigh 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. Reprinted by permission of the publisher.