Repression of TNF-α-induced E-selectin expression by PPAR activators:: Involvement of transcriptional repressor LRF-1/ATF3

被引：49

作者：

Nawa, T

Nawa, MT

Cai, Y

Zhang, C

Uchimura, I

Narumi, S

Numano, F

Kitajima, S

机构：

[1] Tokyo Med & Dent Univ, Med Res Inst, Dept Biochem Genet, Bunkyo Ku, Tokyo 1138510, Japan

[2] Tokyo Med & Dent Univ, Fac Med, Dept Internal Med, Bunkyo Ku, Tokyo 1138510, Japan

[3] Univ Tokyo, Sch Med, Dept Mol Prevent Med, Bunkyo Ku, Tokyo 1130033, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2000年 / 275卷 / 02期

关键词：

D O I：

10.1006/bbrc.2000.3332

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-activated receptor (PPAR) activators were shown to inhibit the expression of E-selectin of human vascular endothelial cells in response to tumor necrosis factor-alpha (TNF-alpha). Troglitazone, pioglitazone, alpha-clofibrate, and 15-deoxy-Delta 12,14-prostaglandin J2 all inhibited the TNF-alpha-stimulated E-selectin gene transcription in reporter assay. To further clarify the underlying transcriptional regulation, nuclear factor(s) that binds to the nuclear factor-endothelial leukocyte adhesion molecule 1 (NF-ELAM1) site of the E-selectin gene promoter was investigated. The activators caused a significant induction of liver regenerating factor 1 (LRF1)/activating transcription factor 3 (ATF3), which bound to the NF-ELAM1 site and repressed the TNF-alpha-induced E-selectin gene expression. From these data, the effect of PPAR activators was mediated, in part, through the induction of LRF1/ATF3. This might provide a novel molecular mechanism of antiinflammatory effect of PPAR activators. (C) 2000 Academic Press.

引用

页码：406 / 411

页数：6

共 37 条

[1] TUMOR-NECROSIS-FACTOR AND INTERLEUKIN-1 LEAD TO PHOSPHORYLATION AND LOSS OF I-KAPPA-B-ALPHA - A MECHANISM FOR NF-KAPPA-B ACTIVATION [J].