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01-12-2007

PPARα Ligands Reduce PCB-Induced Endothelial Activation: Possible Interactions in Inflammation and Atherosclerosis

Authors: Xabier Arzuaga, Gudrun Reiterer, Zuzana Majkova, Michael W. Kilgore, Michal Toborek, Bernhard Hennig

Published in: Cardiovascular Toxicology | Issue 4/2007

Abstract

Exposure to polychlorinated biphenyls (PCBs) can activate inflammatory responses in vascular endothelial cells. Activation of peroxisome proliferator-activated receptors (PPARs) by nutrients or synthetic agonists has been shown to block pro-inflammatory responses both in vitro and in vivo. Here we demonstrate that activation of PPARα by synthetic agonists can reduce 3,3′4,4′-tetrachlorobiphenyl (PCB77)-induced endothelial cell activation. Primary vascular endothelial cells were pretreated with the PPARα ligands fenofibrate or WY14643 followed by exposure to PCB77. PPARα activation protected endothelial cells against PCB77-induced expression of the pro-inflammatory proteins vascular cell adhesion molecule-1 (VCAM-1), cycloxygenase-2 (COX-2), and PCB77-induced expression and activity of the aryl hydrocarbon receptor (AHR) responsive cytochrome P450 1A1 (CYP1A1). Furthermore, basal AHR expression was downregulated by fenofibrate and WY14643. We also investigated the possible interactions between PCBs, and basal PPAR activity and protein expression. Treatment with PCB77 significantly reduced basal mRNA expression of PPARα and the PPAR responsive gene CYP4A1, as well as PPARα protein expression. Also, PCB77 exposure caused a significant decrease in basal PPAR-dependent reporter gene expression in MCF-7 cells. Overall, these findings suggest that PPARα agonists can reduce PCB77 induction of endothelial cell activation by inhibition of the AHR pathway, and that coplanar PCB induced pro-inflammatory effects could be mediated, in part, by inhibition of PPARα expression and function.

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Title: PPARα Ligands Reduce PCB-Induced Endothelial Activation: Possible Interactions in Inflammation and Atherosclerosis
Authors: Xabier Arzuaga
Gudrun Reiterer
Zuzana Majkova
Michael W. Kilgore
Michal Toborek
Bernhard Hennig
Publication date: 01-12-2007
Publisher: Humana Press Inc
Published in: Cardiovascular Toxicology / Issue 4/2007
Print ISSN: 1530-7905
Electronic ISSN: 1559-0259
DOI: https://doi.org/10.1007/s12012-007-9005-8

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PPARα Ligands Reduce PCB-Induced Endothelial Activation: Possible Interactions in Inflammation and Atherosclerosis

Abstract

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Abstract

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