Regulation of intercellular adhesion molecule-1 by dexamethasone in
a human vascular endothelial cell line, eahy926.
Burke-Gaffney, Anne, and Paul G. Hellewell.
Department of Applied Pharmacology, National Heart and Lung
Institute, Dovehouse St., London, SW3 6LY, U.K., Tel. No. (44) 71
-3518170. Fax No. (44) 71-3518270
APStracts 2:0325C, 1995.
Regulation by dexamethasone of intercellular adhesion molecule-1
(ICAM-1) in cultured monolayers of a human umbilical vein endothelial
cell line EAhy926, was investigated. Tumor necrosis factor-[alpha]
(TNF[alpha]) and interferon-_ (IFN_) in combination or
lipopolysaccharide (LPS) alone gave time- and dose-dependent
increases in ICAM-1. Sustained expression of ICAM-1 following short
exposure (30 min) to TNF[alpha]/IFN_ but not to LPS, was observed.
LPS-induced ICAM-1 expression was not inhibited by IL-1 receptor
antagonist (0.01 - 100 [mu]g/ml). Dexamethasone (1000 nM) did not
inhibit TNF[alpha]/IFN_-induced ICAM-1 expression or mRNA induction.
In contrast, dexamethasone dose-dependently (0.1-1000nM) inhibited
LPS-induced ICAM-1 expression, however its effect on mRNA was not
established since ICAM-1 mRNA induced by LPS was not detected at the
time points investigated in this study (3h and 20h). Adhesion of
unstimulated human neutrophils to EAhy926 monolayers activated with
TNF[alpha]/IFN_ or LPS was increased in the presence of dexamethasone
at low doses, whereas neutrophil adhesion to LPS- but not cytokine
-stimulated EC was significantly reduced (P <0.05) in the
presence of a high dose of dexamethasone (1000nM). In conclusion,
dexamethasone was demonstrated to regulate the expression and
function of ICAM-1 in a stimulus-dependent manner.
Received 18 January 1995; accepted in final form 1 September
1995.
APS Manuscript Number C35-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 September 1995.