Estrogen attenuates vascular expression of inflammation associated genes and adhesion of monocytes to endothelial cells.
OBJECTIVE
Investigate effects of estrogen at gene expression and functional levels in vascular wall cells treated with bacterial lipopolysaccharide (LPS).


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.


CONCLUSIONS
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.
Gao
H
H
Department of Medical Nutrition and Biosciences, Karolinska Institute, Novum, 141 86, Huddinge, Sweden.
Liang
M
M
Bergdahl
A
A
Hamrén
A
A
Lindholm
M W
MW
Dahlman-Wright
K
K
Nilsson
B-O
BO
D000818:Animals; D001011:Aorta / Q000473:pathology; D002448:Cell Adhesion; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000166:cytology*; D004730:Endothelium, Vascular / Q000473:pathology; D004958:Estradiol / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation; D007249:Inflammation / Q000473:pathology*; D008070:Lipopolysaccharides / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004967:Estrogens; D008070:Lipopolysaccharides; D004958:Estradiol