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 cell line EAhy926 was investigated. Tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) in combination or lipopolysaccharide (LPS) alone gave time- and dose-dependent increases in ICAM-1. Sustained expression of ICAM-1 was observed after short exposure (30 min) to TNF-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 micrograms/ml). Dexamethasone (1,000 nM) did not inhibit TNF-alpha + IFN-gamma-induced ICAM-1 expression or mRNA induction. In contrast, dexamethasone dose dependently (0.1-1,000 nM) inhibited LPS-induced ICAM-1 expression; 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 neutrophil 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 demonstrated to regulate the expression and function of ICAM-1 in a stimulus-dependent manner.
Burke-Gaffney
A
A
Department of Applied Pharmacology, National Heart and Lung Institute, London, United Kingdom.
Hellewell
P G
PG
D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D003907:Dexamethasone