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, progesterone, and dexamethasone on cytokine-stimulated endothelial cell expression of adhesion molecules. TNF-alpha (250 U/mL) and IL-1 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 with TNF-alpha increased expression of E-selectin (P < 0.03) was noted with beta-estradiol. Strong suppression of ICAM-1 (P < 0.005) and E-selectin (P < 0.005) expression was evident with dexamethasone, which did not influence VCAM-1 expression. After 6 hr stimulation with IL-1 alpha 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 stimulation with IL-1 alpha or TNF-alpha none of the examined steroids showed a significant effect on the fluorescence intensity of adhesion molecules, although there was a slight increase of the percentage of ICAM-1 positive cells with high concentrations of beta-estradiol after stimulation with TNF-alpha. Beta-estradiol and progesterone are modulatory factors of E-selectin expression on endothelial cell in vitro. Dexamethasone reduces adhesion molecule expression over endothelial cells after cytokine stimulation. These effects may be important in understanding the role of these steroids in autoimmune diseases.
Immunopathology Department, Prince Henry Hospital, School of Pathology, University of New South Wales, Anzac Parade, Little Bay, New South Wales, Australia.
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Aziz
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Wakefield
D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D019040:E-Selectin / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D007375:Interleukin-1 / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*
D019040:E-Selectin; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D011374:Progesterone; D004958:Estradiol; D003907:Dexamethasone