title: PPARalpha and PPARdelta activators inhibit cytokine-induced nuclear translocation of NF-kappaB and expression of VCAM-1 in EAhy926 endothelial cells.
abstract: Endothelium injury is a primary event in atherogenesis, which is followed by monocyte infiltration, macrophage differentiation, and smooth muscle cell migration. Peroxisome proliferator-activated receptors (PPARs) are transcription factors now recognized as important mediators in the inflammatory response. The aim of this study was to develop a human endothelial model to evaluate anti-inflammatory properties of PPAR activators. PPAR proteins (alpha, delta and gamma) are expressed in EAhy926 endothelial cells (ECs). Pirinixic acid (Wy-14643), fenofibrate, fenofibric acid, the Merck ligand PPARdelta activator L-165041, 15-deoxy-Delta(12,14)-prostaglandin J2, but not rosiglitazone (BRL-49653) inhibited the induced expression of vascular cell adhesion molecule-1 (VCAM-1), as measured by enzyme linked immunosorbent assay (ELISA), and monocyte binding to activated-EAhy926 cells. The PPARdelta activator L-165041 had the greatest potency to reduce cytokine-induced monocyte chemotactic protein-1 (MCP-1) secretion. All PPAR activators tested which impaired VCAM-1 expression reduced significantly nuclear p65 amount. These results show that EAhy926 endothelial cells are an adequate tool to substantiate and characterize inflammatory impacts of PPAR activators.
authors.affiliation: Centre de Recherche Pierre Fabre, 17 Avenue Jean Moulin, 81106 Cédex, Castres, France. yves.rival@pierre-fabre.com
authors.forename: Yves
authors.initials: Y
authors.lastname: Rival
authors.forename: Nathalie
authors.initials: N
authors.lastname: Benéteau
authors.forename: Thierry
authors.initials: T
authors.lastname: Taillandier
authors.forename: Mylène
authors.initials: M
authors.lastname: Pezet
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Dupont-Passelaigue
authors.forename: Jean François
authors.initials: JF
authors.lastname: Patoiseau
authors.forename: Didier
authors.initials: D
authors.lastname: Junquéro
authors.forename: Francis C
authors.initials: FC
authors.lastname: Colpaert
authors.forename: André
authors.initials: A
authors.lastname: Delhon
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D021581:Active Transport, Cell Nucleus; D001665:Binding Sites; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D020025:Peroxisome Proliferators / Q000494:pharmacology*; D010636:Phenols / Q000494:pharmacology*; D010642:Phenoxyacetates; D011743:Pyrimidines / Q000494:pharmacology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*
chemical_list: C520164:4-(3-(2-propyl-3-hydroxy-4-acetyl)phenoxy)propyloxyphenoxy acetic acid; D000085:Acetates; D018932:Chemokine CCL2; D016207:Cytokines; D016328:NF-kappa B; D020025:Peroxisome Proliferators; D010636:Phenols; D010642:Phenoxyacetates; D011743:Pyrimidines; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C006253:pirinixic acid