PPARalpha and PPARdelta activators inhibit cytokine-induced nuclear translocation of NF-kappaB and expression of VCAM-1 in EAhy926 endothelial cells
Autor: | Thierry Taillandier, Didier Junquero, Andre Delhon, Nathalie Benéteau, Mylène Pezet, Francis Colpaert, Yves Rival, Jean Francois Patoiseau, Elisabeth Dupont-Passelaigue |
---|---|
Rok vydání: | 2002 |
Předmět: |
medicine.medical_specialty
Endothelium Smooth muscle cell migration medicine.medical_treatment Active Transport Cell Nucleus Peroxisome proliferator-activated receptor Down-Regulation Gene Expression Receptors Cytoplasmic and Nuclear Vascular Cell Adhesion Molecule-1 Biology Acetates Phenoxyacetates Monocytes chemistry.chemical_compound Phenols Internal medicine medicine Humans VCAM-1 Cells Cultured Chemokine CCL2 Pharmacology chemistry.chemical_classification Cell Nucleus Binding Sites Activator (genetics) Monocyte NF-kappa B Intercellular Adhesion Molecule-1 Cell biology medicine.anatomical_structure Cytokine Endocrinology Pyrimidines chemistry Pirinixic Acid Cytokines Peroxisome Proliferators Endothelium Vascular Signal Transduction Transcription Factors |
Zdroj: | European journal of pharmacology. 435(2-3) |
ISSN: | 0014-2999 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |