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Am J Physiol Gastrointest Liver Physiol 277: G572-G576, 1999;
0193-1857/99 $5.00
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Vol. 277, Issue 3, G572-G576, September 1999

Role of inducible nitric oxide synthase in the regulation of VCAM-1 expression in gut inflammation

Shigeyuki Kawachi1, Adam Cockrell1, F. Stephen Laroux1, Laura Gray1, D. Neil Granger1, Henri C. van der Heyde2, and Matthew B. Grisham1

Departments of 1 Molecular and Cellular Physiology and 2 Microbiology and Immunology, Louisiana State University Medical Center, Shreveport, Louisiana 71130

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 µg/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 µg/kg TNF-alpha further enhanced VCAM-1 expression by approximately twofold compared with wild-type mice injected with 10 µg/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+, 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.

neutrophils; nuclear factor-kappa B; endothelium


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