Down-regulation of endothelial cell estrogen receptor expression by the inflammation promoter LPS

Endothelial cells express both estrogen receptor (ER) alpha and beta. The objective of this study was to investigate if and how mediators of inflammation regulate endothelial cell ER alpha and ER beta expression ER alpha and ER beta transcript and protein expression were determined by real-time quantitative PCR and Western blotting, respectively, in endothelial cell line bEnd.3 cells stimulated with the inflammation promoter lipopolysaccharide (E coli LPS). Stimulation with LPS (500 ng/ml and 10 mu g/ml) for 4 days reduced both ER alpha and ER beta mRNA levels The glucocorticoid dexamethasone (1 mu M) had no effect on LPS-induced attenuation of ER alpha and beta transcript expression Full-length 66-67 kDa ER alpha protein was unaffected by 4 days stimulation with LPS, while the 46-kDa ER alpha isoform was reduced by about 20% ER beta protein was reduced by about 40% by LPS at 4 days Treatment with 17 beta-estradiol (E-2, 100 nM) for 4 days increased ER beta mRNA by about 8 times but had no effect on ER alpha mRNA level. The E-2-induced increase in ER beta transcript was not associated with increased ER beta protein E-2 increased ER beta mRNA expression also in the presence of LPS, suggesting that inflammation-induced impairment of ER beta signalling is rescued by estrogen (C) 2010 Elsevier Ireland Ltd. All rights reserved.