ABSTRACT
OBJECTIVE: Investigate effects of estrogen at gene expression and functional levels in vascular wall cells treated with bacterial lipopolysaccharide (LPS). MATERIALS AND METHODS: Aortic segments from ovariectomized mice were treated with LPS for 24 h in the absence or presence of 17beta-estradiol (E2). Gene activity was determined by Affymetrix microarray analysis and real-time RT-PCR. Adhesion of [3H]-thymidine labelled human THP-1 monocytes to mouse bEnd.3 endothelial cells was determined by measuring radioactivity of DNA from co-culture homogenates. RESULTS: Analysis of global gene expression profiles revealed that 10 nM E2 attenuates LPS-induced (10 ng/ml) expression of genes coding for well-known acute-phase proteins, such as alpha-trypsin inhibitor heavy chain 4, serum amyloid A3 and lipocalin 2. The E2-induced down-regulation of these three genes observed by microarray was confirmed by realtime RT-PCR. Treatment with 500 ng/ml LPS increased adhesion of monocytes to endothelial cells more than two fold. Importantly, LPS-induced monocyte adhesion was fully prevented by 50 nM E2. CONCLUSION: Estrogen reduces expression of acute-phase protein genes and inhibits LPS-induced moncocyte adhesion to endothelial cells, suggesting that estrogen might have a vasculoprotective effect via this mechanism.
