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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:2568-2575.)
© 1997 American Heart Association, Inc.

Articles

Regulation of Tumor Necrosis Factor- and Interleukin-1ß Induced Adhesion Molecule Expression in Human Vascular Smooth Muscle Cells by cAMP

Marina Braun; Peter Pietsch; Angela Zepp; Karsten Schrör; Gert Baumann; ; Stephan B. Felix

From the Medizinische Klinik I, Universitätsklinikum Charité, Humboldt-Universität zu Berlin. Germany (M.B., P.P., A.Z., G.B., S.B.F.), and the Institut für Pharmakologie, Heinrich-Heine-Universität, Düsseldorf, Germany (K.S.)

Correspondence to Dr Marina Braun, Universitätsklinikum Charité, Kardiologisches Forschungslabor, Ziegelstraße 5-9, D-10117 Berlin, Germany. E-mail mbraun{at}rz.charite.hu-berlin.de.

Abstract This study investigates the hypothesis that the elevation of intracellular cAMP may affect cytokine-induced expression of adhesion molecules on human vascular smooth muscle cells. In cultured human smooth muscle cells from coronary arteries and saphenous veins, tumor necrosis factor- (TNF-) and interleukin-1ß (IL-1ß) induced the expression of intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1), whereas interferon- (INF-) selectively stimulated the expression of ICAM-1. Adenylyl cyclase was stimulated either by the stable prostacyclin mimetic cicaprost or by forskolin. Adhesion molecules were detected by a cell surface enzyme immunoassay and the respective mRNA by reverse transcriptase polymerase chain reaction (rt-PCR). Cicaprost as well as forskolin significantly inhibited TNF-- and IL-1ß-induced cell surface expression of ICAM-1 and VCAM-1. Semiquantitative rt-PCR measurements showed a marked decrease of TNF-- and IL-1ß-induced mRNA levels of both adhesion molecules after preincubation with cicaprost. The stability of TNF--induced ICAM-1 and VCAM-1 expression at mRNA and protein level was not altered by cicaprost. The IFN--induced increase of cell surface expression of ICAM-1 and the respective mRNA levels, however, were not significantly altered by elevation of intracellular cAMP. Basal and stimulated cAMP levels, measured by radioimmunoassay, did not differ in TNF-- and IFN-treated cells. The present results demonstrate that the expression of adhesion molecules on human smooth muscle cells induced by cytokines is differentially modulated by activation of adenylyl cyclase.

Key Words: smooth muscle cells • adhesion molecules • human • cAMP

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