REGULATION OF TUMOR-NECROSIS-FACTOR-ALPHA AND INTERLEUKIN-1-BETA INDUCED ADHESION MOLECULE EXPRESSION IN HUMAN VASCULAR SMOOTH-MUSCLE CELLSBY CAMP

This study investigates the hypothesis that the elevation of intracell ular cAMP may affect cytokine-induced expression of adhesion molecules on human vascular smooth muscle cells. In cultured human smooth muscl e cells from coronary arteries and saphenous veins, tumor necrosis fac tor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) induced the e xpression of intercellular adhesion molecule (ICAM-1) and vascular cel l adhesion molecule (VCAM-1), whereas interferon-gamma (INF-gamma) sel ectively stimulated the expression of ICAM-1. Adenylyl cyclase was sti mulated either by the stable prostacyclin mimetic cicaprost or by fors kolin. Adhesion molecules were detected by a cell surface enzyme immun oassay and the respective mRNA by reverse transcriptase polymerase cha in reaction (rt-PCR). Cicaprost as well as forskolin significantly inh ibited TNF-alpha- and IL-1 beta-induced cell surface expression of ICA M-1 and VCAM-1. Semiquantitative rt-PCR measurements showed a marked d ecrease of TNF-alpha- and IL-1 beta-induced mRNA levels of both adhesi on molecules after preincubation with cicaprost. The stability of TNF- alpha-induced ICAM-1 and VCAM-1 expression at mRNA and protein level w as not altered by cicaprost. The IFN-gamma-induced increase of cell su rface expression of ICAM-1 and the respective mRNA levels, however, we re not significantly altered by elevation of intracellular cAMP. Basal and stimulated cAMP levels, measured by radioimmunoassay, did not dif fer in TNF-alpha- and IFN gamma-treated cells. The present results dem onstrate that the expression of adhesion molecules on human smooth mus cle cells induced by cytokines is differentially modulated by activati on of adenylyl cyclase.