Peroxisome proliferator-activated receptor (PPAR) α and δ activators induce ICAM-1 expression in quiescent non stimulated endothelial cells

Journal of Inflammation

Research

Nadja Zöller¹  Tsige Hailemariam-Jahn¹  Roland Kaufmann¹  Stefan Kippenberger¹  Johannes Kleemann¹  Julia Naidenow¹  Monika Doll¹  Victoria Lang¹  Igor Hrgovic¹  Markus Meissner¹ 

[1] Department of Dermatology, Venereology and Allergology, Johann Wolfgang Goethe-University, Theodor-Stern-Kai 7, D-60590, Frankfurt am Main, Germany;

关键词: PPARα;    PPARδ;    mRNA stability;    ICAM-1;    Endothelial cell;    Sp1;    Promoter;   

DOI  :  10.1186/s12950-016-0135-2

 received in 2016-02-11, accepted in 2016-08-10,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundPeroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that are implicated in the regulation of lipid and glucose homeostasis. PPAR agonists have been shown to control inflammatory processes, in part by inhibiting the expression of distinct proinflammatory genes such as vascular cell adhesion molecule-1 (VCAM-1), IL-8, and intercellular adhesion molecule-1 (ICAM-1). ICAM-1 is an important endothelial membrane receptor that facilitates the transmigration of leukocytes across the endothelium. To date, the influence of PPARα and δ activators on the expression of ICAM-1 in non-induced, quiescent endothelial cells has been unclear. Therefore, we examined the effects of various PPARα and δ agonists on the expression of ICAM-1 in non-stimulated primary human endothelial cells.ResultsWe found that PPARα and PPARδ agonists significantly induced ICAM-1 surface, intracellular protein, and mRNA expression in a time and concentration-dependent manner. The PPARδ induced ICAM-1 expression could be paralleled with a significantly increased T-cell adherence to the endothelial cells whereas PPARα failed to do so. Transcriptional activity studies using an ICAM-1 reporter gene constructs revealed that PPARδ, but not PPARα agonists induced gene expression by stimulating ICAM-1 promoter activity via an Sp1 transcription factor binding site and inhibit the binding of the transcription factors Sp1 and Sp3. Furthermore, we performed mRNA stability assays and found that PPARα and PPARδ agonists increased ICAM-1 mRNA stability.ConclusionTherefore, our data provide the first evidence that PPARα and PPARδ agonists induce ICAM-1 expression in non-stimulated endothelial cells via transcriptional and posttranscriptional mechanisms.

【 授权许可】

CC BY   
© The Author(s). 2016