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

The objectives of this study were to assess the role of the inducible isofo rm of nitric oxide synthase (iNOS) on vascular cell adhesion molecule I (VC AM-1) expression in vivo in an acute model of inflammation induced in iNOS- deficient (iNOS(-/-)) mice and compare these data to those obtained by phar macological inhibition of iNOS in a CD4(+) T lymphocyte-dependent model of chronic colitis. VCAM-1 expression was quantified in vivo using the dual ra diolabel monoclonal antibody technique. We found that intraperitoneal injec tion of 10 mu g/kg tumor necrosis factor-a (TNF-alpha) enhanced VCAM-1 expr ession by approximately twofold in the colon, cecum, and stomach but not sm all intestine in iNOS(-/-) mice compared with TNF-alpha-injected wild-type mice. Injection of wild-type mice with 25 mu g/kg TNF-alpha further enhance d VCAM-1 expression by approximately twofold compared with wild-type mice i njected with 10 mu g/kg TNF-alpha; however, VCAM-1 expression was not furth er enhanced in any gastrointestinal organ system in iNOS(-/-) mice. In a se cond series of experiments, we found that continuous inhibition of iNOS usi ng oral administration of N-G-iminoethyl-L-lysine did not alter the enhance d 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 infl ammation; however, this effect is modest and tissue specific and occurs onl y when VCAM-1 expression is submaximal, iNOS does not appear to modulate VC AM-1 expression in an immune model of chronic colitis.