REGULATION OF ICAM-1 BY DEXAMETHASONE IN A HUMAN VASCULAR ENDOTHELIAL-CELL LINE EAHY926

Regulation by dexamethasone of intercellular adhesion molecule-1 (ICAM -1) in cultured monolayers of the human umbilical vein endothelial cel l line EAhy926 was investigated Tumor necrosis factor-a (TNF-alpha) an d interferon-gamma (IFN-gamma) in combination or lipopolysaccharide (L PS) alone gave time- and dose-dependent increases in ICAM-1. Sustained expression of ICAM-1 was observed after short exposure (30 min) to TN F-alpha + IFN-gamma, but not to LPS. LPS-induced ICAM-1 expression was not inhibited by interleukin-1 (IL-1) receptor antagonist (0.01-100 m u g/ml). Dexamethasone (1,000 nM) did not inhibit TNF-alpha + IFN-gamm a-induced ICAM-1 expression or mRNA induction. In contrast, dexamethas one dose dependently (0.1-1,000 nM) inhibited LPS-induced ICAM-1 expre ssion; however, its effect on mRNA was not established, because ICAM-1 mRNA induced by LPS was not detected at the time points investigated in this study (3 and 20 h). Adhesion of unstimulated human neutrophils to EAhy926 monolayers activated with TNF-alpha + IFN-gamma or LPS was increased in the presence of dexamethasone at low doses, whereas neut rophil adhesion to LPS- but not cytokine-stimulated endothelial cells was significantly reduced (P <0.05) in the presence of a high dose of dexamethasone (1,000 nM). In conclusion, dexamethasone was demonstrate d to regulate the expression and function of ICAM-1 in a stimulus-depe ndent manner.