CYCLO-OXYGENASE-2 REGULATES INDUCIBLE ICAM-1 AND VCAM-1 EXPRESSION INHUMAN VASCULAR SMOOTH-MUSCLE CELLS

Prostaglandins are well characterised inflammatory mediators, whose fo rmation is regulated by constitutive (COX-1) or inducible (COX-2) isof orms of cyclooxygenase. We have previously demonstrated that IL-1 beta causes an induction of COX-2 in human vascular smooth muscle (1). Thi s present study investigates the ability of different cytokines to ind uce ICAM-1 and VCAM-1 on human vascular smooth muscle, and tests wheth er co-induced COX-2 would regulate their expression. IL-1 beta induced ICAM-1, and COX activity, while it had no affect on VCAM-1. Conversel y, IL-4 induced VCAM-1, while it had no effect on PGE(2) release or IC AM-1 expression. Inhibition of IL-1 beta induced COX-2 and elevated IC AM-1 expression, an effect reversed by exogenous PGE2. Furthermore, IL -1 beta inhibited IL-4 induced VCAM-1 expression, which was also rever sed by COX-2 inhibition. These results demonstrate that COX-2 limits a dhesion molecule expression on human vascular smooth muscle cells and suggest that COX-2 can play a protective role in cardiovascular and in flammatory diseases. (C) 1998 Academic Press.