Title

Effects of 17 β-estradiol on lipopolysacharride-induced intracellular adhesion molecule-1 mRNA expression and Ca2+ homeostasis alteration in human endothelial cells

Document Type

Article

Publication Title

Vascular Pharmacology

ISSN

1537-1891

Volume

53

Issue

5-6

DOI

10.1016/j.vph.2010.09.001

First Page

230

Last Page

238

Publication Date

11-1-2010

Abstract

Recent evidence showed that 17 β-estradiol (E ) decreased cytokine-induced expression of cell adhesion molecules (CAM). Changes in intracellular Ca concentration ([Ca ] ) has been shown to be associated with CAM expression in endothelial cells. Here, the effects of E (1μM, 24h) on the expression of intracellular adhesion molecule-1 (ICAM-1) and [Ca ] were investigated in a lipopolysaccharide (LPS) (100ng/mL, 18h)-stimulated human endothelial cell line, EA.hy926, using real-time PCR and spectrofluorometry, respectively. PCR analysis revealed a significant increase in ICAM-1 expression in calcium ionophore A23187 (1nM)- or LPS-stimulated cells. Pretreatment of cells with E significantly inhibited LPS-induced ICAM-1 mRNA expression. [Ca ] was monitored in Fura-2AM-loaded cells in the presence and absence of extracellular Ca with thapsigargin (TG, 1μM), a sarco/endoplasmic reticulum ATPase inhibitor or ATP (100μM). The extent of TG- or ATP-induced [Ca ] increase was significantly higher in LPS-stimulated cells than in control cells. Pre-treatment of LPS-stimulated cells with E limited the Ca response to the same level as in control cells. Furthermore, ICI 182,780, an estrogen receptor antagonist, attenuated the inhibitory actions of E on ICAM-1 mRNA expression and Ca responses, suggesting that estrogen receptors mediate, at least in part, the effects of estrogen. These data suggest a potential underlying mechanism for the protective effect of E against atherosclerosis. © 2010 Elsevier Inc. 2 i 2 i 2 i i 2 2 2 2+ 2+ 2+ 2+ 2+ 2+ 2+ 2+

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