title: Quercetin blocks caveolae-dependent pro-inflammatory responses induced by co-planar PCBs.
abstract: Polychlorinated biphenyls (PCBs) are widespread environmental contaminants, and co-planar PCBs can induce oxidative stress and activation of pro-inflammatory signaling cascades which are associated with atherosclerosis. The majority of the toxicological effects elicited by the co-planar PCB exposure are associated to the activation of the aryl hydrocarbon receptor (AHR) and subsequent induction of responsive genes. Previous studies from our group have shown that quercetin, a nutritionally relevant flavonoid can significantly reduce PCB77 induction of oxidative stress and expression of the AHR responsive gene cytochrome P450 1A1 (CYP1A1). We also have evidence that membrane domains called caveolae may regulate PCB-induced inflammatory parameters. Thus, we hypothesized that quercetin can modulate PCB-induced endothelial inflammation associated with caveolae. To test this hypothesis, endothelial cells were exposed to co-planar PCBs in combination with quercetin, and the expression of pro-inflammatory genes was analyzed by real-time PCR. Quercetin co-treatment significantly blocked both PCB77 and PCB126 induction of CYP1A1, vascular cell adhesion molecule 1 (VCAM-1), E-selectin and P-selectin. Exposure to PCB77 also induced caveolin-1 protein expression, which was reduced by co-treatment with quercetin. Our results suggest that inflammatory pathways induced by co-planar PCBs can be down-regulated by the dietary flavonoid quercetin through mechanisms associated with functional caveolae.
authors.affiliation: Molecular and Cell Nutrition Laboratory, College of Agriculture, University of Kentucky, Lexington KY 40536-0200, USA.
authors.forename: Yean Jung
authors.initials: YJ
authors.lastname: Choi
authors.forename: Xabier
authors.initials: X
authors.lastname: Arzuaga
authors.forename: Chase T
authors.initials: CT
authors.lastname: Kluemper
authors.forename: Adelka
authors.initials: A
authors.lastname: Caraballo
authors.forename: Michal
authors.initials: M
authors.lastname: Toborek
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hennig
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D021941:Caveolae / Q000378:metabolism*; D051242:Caveolin 1 / Q000096:biosynthesis; D002478:Cells, Cultured; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis; D019040:E-Selectin / Q000096:biosynthesis; D042783:Endothelial Cells / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000139:chemically induced*; D019007:P-Selectin / Q000096:biosynthesis; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D011794:Quercetin / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
chemical_list: D000893:Anti-Inflammatory Agents; D051242:Caveolin 1; D019040:E-Selectin; D019007:P-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D011794:Quercetin; D011078:Polychlorinated Biphenyls; D019363:Cytochrome P-450 CYP1A1