Induction of IκB:: atrial natriuretic peptide as a regulator of the NF-κB pathway

被引:54
|
作者
Kiemer, AK [1 ]
Weber, NC [1 ]
Vollmar, AM [1 ]
机构
[1] Univ Munich, Ctr Drug Res, Dept Pharm, D-81377 Munich, Germany
关键词
cardiovascular hormone; natriuretic peptides; cGMP; NPR-A; adhesion molecules; TNF-alpha; endothelial cells; HUVEC;
D O I
10.1016/S0006-291X(02)00807-0
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
Atrial natriuretic peptide (ANP) was shown to possess anti-inflammatory potential due to its potency to inhibit the production of inflammatory mediators, such as TNF-alpha. The aim of this study was to determine potential effects of ANP on endothelial cells targeted by TNF-alpha. HUVEC were treated with TNF-alpha and expression of adhesion molecules was investigated by FACS and RTPCR. Pre-treatment of cells with ANP (30 min) significantly reduced TNF-alpha-induced cell surface protein and mRNA expression of E-selectin and ICAM-1, whereas it did not influence VCAM-1. ANP reduced TNF-alpha-induced NF-kappaB activity, which was paralleled by a decreased translocation of p65 to nuclei. ANP did not alter TNF-alpha-induced phosphorylation and degradation of IkappaB-alpha, but attenuated degradation of IkappaB-epsilon. Moreover, ANP leads to a transcriptional induction of IkappaB-alpha. The induction of IkappaB by ANP is suggested as a novel mechanism for regulating inflammatory signalling in endothelial cells, leading to reduced TNF-alpha-induced expression of adhesion molecules. (C) 2002 Elsevier Science (USA). All rights reserved.
引用
收藏
页码:1068 / 1076
页数:9
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