Dietary Flavonoids Block PCB-Induced Proinflammatory Responses in Vascular Endothelial Cells.
Xabier Arzuaga1,2, Chase T. Kluemper3, Michal Toborek2,4 and Bernhard Hennig1,2.
Department of Animal and Food Sciences, College of Agriculture1, Graduate Center for Nutritional Sciences2, Department of Biology3, Department of Surgery4, University of Kentucky Lexington 40536-0200, USA.
Polychlorinated biphenyls (PCBs) are widespread environmental contaminants that can cause a wide variety of toxic effects in exposed organisms. Co-planar PCBs can induce oxidative stress and activation of pro-inflammatory signaling cascades which are associated with atherosclerosis. Vascular endothelial cells have been shown to be sensitive to chemical insult and cellular dysfunction after co-planar PCB exposure. The majority of the toxicological effects elicited by co-planar PCB exposure are associated to activation of the aryl hydrocarbon receptor (AHR) and subsequent induction of responsive genes. Quercetin, a dietary flavonoid, has been demonstrated to possess antioxidant and anti-inflammatory properties in various in vivo and in vitro models. Previous studies from our group have shown that flavonoids can significantly reduce PCB77 induction of oxidative stress and expression of the AHR responsive gene cytochrome P450 1A1 (CYP1A1). To determine if the flavonoids quercetin, isorhamnetin and kaempferol can block PCB77 and 126 induced expression of AHR responsive and pro-inflammatory genes associated with atherosclerosis, porcine endothelial cells were exposed to PCB77 or 126 in combination with quercetin, and expression of proinflammatory proteins was analyzed by western blot. Upon confluence, cells were serum deprived for 8 h, then treated with PCB77 (1 µM), quercetin (10 µM), or PCB77 plus quercetin for a period of 16 h. Quercetin co-treatment significantly blocked PCB77 induction of the pro-oxidative and inflammatory proteins: CYP1A1 and vascular cell adhesion molecule 1 (VCAM1). Co-treatment with isorhamnetin or kaempferol altered PCB77 and 126 induced protein expression of the AHR responsive proteins: CYP1A1 and CYP1B1. These results suggest that quercetin, isorhamnetin and kaempferol, can block co-planar PCB activation of the AHR pathway and induction of responsive pro-inflammatory genes. (Supported by grants from NIEHS, NIH (P42ES07380) and the University of Kentucky AES).
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