Quercetin blocks caveolae-dependent pro-inflammatory responses induced by co-planar PCBs

• Published in: Environment international Vol. 36; no. 8; pp. 931 - 934
• Main Authors: Choi, Yean Jung, Arzuaga, Xabier, Kluemper, Chase T., Caraballo, Adelka, Toborek, Michal, Hennig, Bernhard
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Oxford Elsevier Ltd 01.11.2010; Elsevier
• Subjects: Activation; AHR; Anti-Inflammatory Agents - pharmacology; Biological and medical sciences; Cascades; Caveolae; Caveolae - metabolism; Caveolin 1 - biosynthesis; Cell adhesion; Cells, Cultured; Chemical and industrial products toxicology. Toxic occupational diseases; Contaminants; CYP1A1; Cytochrome P-450 CYP1A1 - biosynthesis; E-Selectin - biosynthesis; Endothelial cells; Endothelial Cells - drug effects; Flavonoids; Gene Expression Profiling; Genes; Humans; Inflammation - chemically induced; MAPKs; Medical sciences; P-Selectin - biosynthesis; PCBs; Polychlorinated biphenyls; Polychlorinated Biphenyls - toxicity; Quercetin; Quercetin - pharmacology; Reverse Transcriptase Polymerase Chain Reaction - methods; Stresses; Toxicology; Various organic compounds; Vascular Cell Adhesion Molecule-1 - biosynthesis; VCAM-1; PCBs; VCAM-1; Caveolae; Quercetin; CYP1A1; AHR; MAPKs; Cell culture; Enzyme; Toxicity; Cytochrome P450; Transferases; Mitogen-activated protein kinase; Polychlorobiphenyls; Inflammation; In vitro; Persistent organic pollutant; Prevention; Halogenated hydrocarbon; Chlorine Organic compounds; Chlorocarbon; Aromatic compound; Mechanism of action; Organic compounds
• ISSN: 0160-4120; 1873-6750
• DOI: 10.1016/j.envint.2009.06.009

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.