MODULATION OF ENDOTHELIAL-CELL EXPRESSION OF ICAM-1, E-SELECTIN, AND VCAM-1 BY BETA-ESTRADIOL, PROGESTERONE, AND DEXAMETHASONE

The aim of this study was to examine the effects of beta-estradiol, pr ogesterone, and dexamethasone on cytokine-stimulated endothelial cell expression of adhesion molecules. TNF-alpha (250 U/ml) and IL-l alpha (50 U/ml) were used to stimulate the endothelial cells for 6 or 23 hr in vitro. Indirect immunofluorescence and flow cytometry were used to quantitate expression of adhesion molecules, After 6 hr stimulation wi th TNF-alpha increased expression of E-selectin (P < 0.03) was noted w ith beta-estradiol, Strong suppression of ICAM-1 (P < 0.005) and E-sel ectin (P < 0.005) expression was evident with dexamethasone, which did not influence VCAM-1 expression, After 6 hr stimulation with IL-l alp ha suppression of E-selectin was observed with progesterone (P < 0.001 ). Dexamethasone had strong suppressive effects on ICAM-1 (P < 0.001), E-selectin (P < 0.0001), and VCAM-1 (P < 0.0002), After 23 hr stimula tion with IL-1 alpha or TNF-alpha none of the examined steroids showed a significant effect on the fluorescence intensity of adhesion molecu les, although there was a slight increase of the percentage of ICAM-1- positive cells with high concentrations of beta-estradiol after stimul ation with TNF-alpha. beta-Estradiol and progesterone are modulatory f actors of E-selectin expression on endothelial cell in vitro. Dexameth asone reduces adhesion molecule expression over endothelial cells afte r cytokine stimulation. These effects may be important in understandin g the role of these steroids in autoimmune diseases. (C) 1996 Academic Press, Inc.