RU486 antagonizes the inhibitory effect of peroxisome proliferator-activated receptor α on interleukin-6 production in vascular endothelial cells

被引：11

作者：

Xu, X ^{[1
]}

Otsuki, M ^{[1
]}

Sumitani, S ^{[1
]}

Saito, H ^{[1
]}

Kouhara, H ^{[1
]}

Kasayama, S ^{[1
]}

机构：

[1] Osaka Univ, Dept Mol Med, Grad Sch Med C4, Suita, Osaka 5650871, Japan

来源：

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY | 2002年 / 81卷 / 02期

关键词：

peroxisome proliferator-activated receptor; interleukin-6; RU486; vascular endothelial cells;

D O I：

10.1016/S0960-0760(02)00055-9

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：

Peroxisome proliferator-acitivated receptor alpha (PPARalpha) is a member of nuclear receptor superfamily. Recent studies have shown that the activators for PPARalpha inhibit the expression of some inflammatory molecules in vascular endothelial cells (ECs) and vascular smooth muscle cells, indicating the anti-inflammatory roles of PPARalpha on vascular walls. In this investigation, we showed that RU486, already proved to be an active anti-glucocorticoid and anti-progesterone agent, blocked the inhibition of tumor necrosis factor (TNF)-alpha-stimulated interleukin-6 (IL-6) production by the PPARalpha activator fenofibrate in human umbilical vein ECs. Transient transfection of bovine aortic ECs with an IL-6 promoter construct demonstrated that RU486 blocked the inhibitory effect of fenofibrate on TNF-alpha-induced IL-6 promoter activity. By fluorescence microscopy, RU486 was found to prevent fenofibrate-induced nuclear translocation of PPARalpha. Thus, RU486 has an antagonizing effect on PPARalpha-mediated down-regulation of IL-6 in vascular ECs. This effect may be exerted by its interference with the nuclear translocation of PPARalpha. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：141 / 146

页数：6

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