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Estrogen-mediated protection against HIV Tat protein-induced inflammatory pathways in human vascular endothelial cells.

Abstract：

OBJECTIVE:It has been proposed that human immunodeficiency virus (HIV) infection-induced inflammatory environment may contribute to the pathogenesis of cardiovascular diseases. Recent studies have also demonstrated the potential role of estrogen as therapeutic agents in the prevention or treatment of cardiovascular diseases. In the present study, we assessed the hypothesis that estrogen may attenuate the HIV Tat protein-induced inflammatory pathways in human vascular endothelium. METHODS:Expression of inflammatory mediators in human endothelial cells was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Electrophoretic mobility shift assay (EMSA) also was performed to investigate the DNA-binding activities of several transcription factors, which are known to regulate expression of these inflammatory genes. RESULTS:Acute exposure of human endothelial cells to Tat markedly induced the mRNA and protein expression of IL-1beta, MCP-1, VCAM-1, and E-selectin. Tat also stimulated the adherence of inflammatory cells to endothelial cell monolayers. Significant and dose-dependent increases in NF-kappaB DNA-binding activity were observed in human endothelial cells treated with Tat. However, Tat did not affect DNA-binding activities of AP-1, CREB, and STAT1. Pretreatment with 17beta-estradiol dramatically blocked the activation of NF-kappaB in human endothelial cells exposed to Tat. In addition, 17beta-estradiol selectively inhibited the Tat-induced expression of IL-1beta. CONCLUSION:Our results suggest that estrogen may protect against Tat-induced inflammatory reactions in human vascular endothelium via blocking the NF-kappaB-mediated molecular signaling pathways. These data may contribute to understanding the pathogenesis of cardiovascular complications and development of therapeutic strategies for HIV-infected patients.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Lee YW,Eum SY,Nath A,Toborek M

doi

10.1016/j.cardiores.2004.03.006

subject

Has Abstract

pub_date

2004-07-01 00:00:00

pages

139-48

issue

eissn

0008-6363

issn

1755-3245

pii

S0008636304001221

journal_volume

pub_type

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Estrogen-mediated protection against HIV Tat protein-induced inflammatory pathways in human vascular endothelial cells.