TNF-α stimulation of MCP-1 expression is mediated by the Akt/PKB signal transduction pathway in vascular endothelial cells

被引：80

作者：

Murao, K ^{[1
]}

Ohyama, T

Imachi, H

Ishida, T

Cao, WM

Namihira, H

Sato, M

Wong, NCW

Takahara, J

机构：

[1] Kagawa Med Univ, Dept Internal Med 1, Miki, Kagawa 7610793, Japan

[2] Univ Calgary, Fac Med, Dept Med, Calgary, AB T2N 4N1, Canada

[3] Univ Calgary, Fac Med, Dept Biochem & Mol Biol, Calgary, AB T2N 4N1, Canada

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2000年 / 276卷 / 02期

关键词：

MCP-1; Akt; TNF-alpha; HUVECs; wortmannin; transcription;

D O I：

10.1006/bbrc.2000.3497

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

MCP-1 is expressed in a variety of cell types including vascular endothelial cells following induction by different stimuli such as tumor necrosis factor (TNF)-alpha. Although TNF-alpha stimulates MCP-1 expression and secretion, the mechanism by which TNF-alpha stimulates expression of the MCP-1 gene is not known. In this study, we examine the involvement of the phosphatidylinositol-3-OH kinase (PI3-kinase)-Akt/PKB pathway. Exposure of human umbilical vein endothelial cells (HUVECs) to TNF-alpha elicited the rapid phosphorylation of Akt/PKB. In HUVECs, wortmannin, a PI3-kinase inhibitor, inhibits TNF-alpha-mediated MCP-1 secretion at a dose dependent manner. Constitutively active form of Akt/PKB induces transcription of the MCP-1 gene, and cotransfection of dominant negative Akt/PKB suppressed the activation of the MCP-1 promoter induced by TNF-alpha. These findings show that Akt/PKB participates in the TNF-alpha induction of MCP-1 gene transcription in endothelial cells. (C) 2000 Academic Press.

引用

页码：791 / 796

页数：6

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