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Title: EGCG protects endothelial cells against PCB 126-induced inflammation through inhibition of AhR and induction of Nrf2-regulated genes

Abstract

Tea flavonoids such as epigallocatechin gallate (EGCG) protect against vascular diseases such as atherosclerosis via their antioxidant and anti-inflammatory functions. Persistent and widespread environmental pollutants, including polychlorinated biphenyls (PCB), can induce oxidative stress and inflammation in vascular endothelial cells. Even though PCBs are no longer produced, they are still detected in human blood and tissues and thus considered a risk for vascular dysfunction. We hypothesized that EGCG can protect endothelial cells against PCB-induced cell damage via its antioxidant and anti-inflammatory properties. To test this hypothesis, primary vascular endothelial cells were pretreated with EGCG, followed by exposure to the coplanar PCB 126. Exposure to PCB 126 significantly increased cytochrome P450 1A1 (Cyp1A1) mRNA and protein expression and superoxide production, events which were significantly attenuated following pretreatment with EGCG. Similarly, EGCG also reduced DNA binding of NF-κB and downstream expression of inflammatory markers such as monocyte chemotactic protein-1 (MCP-1) and vascular cell adhesion protein-1 (VCAM-1) after PCB exposure. Furthermore, EGCG decreased endogenous or base-line levels of Cyp1A1, MCP-1 and VCAM-1 in endothelial cells. Most of all, treatment of EGCG upregulated expression of NF-E2-related factor 2 (Nrf2)-controlled antioxidant genes, including glutathione S transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1), in a dose-dependent manner.more » In contrast, silencing of Nrf2 increased Cyp1A1, MCP-1 and VCAM-1 and decreased GST and NQO1 expression, respectively. These data suggest that EGCG can inhibit AhR regulated genes and induce Nrf2-regulated antioxidant enzymes, thus providing protection against PCB-induced inflammatory responses in endothelial cells. -- Highlights: ► PCBs cause endothelial inflammation and subsequent atherosclerosis. ► Nutrition can modulate toxicity by environmental pollutants. ► We demonstrated that EGCG can decrease PCB-induced inflammation. ► EGCG protection was via inhibition of AhR and induction of Nrf2 regulatory genes.« less

Authors:
 [1];  [2];  [3];  [4];  [1];  [2]
  1. Superfund Research Program, University of Kentucky, Lexington, KY 40536 (United States)
  2. (United States)
  3. Department of Pathology, College of Medicine, University of Iowa, Iowa City, IA 52242 (United States)
  4. Department of Neurosurgery, University of Kentucky, Lexington, KY 40536 (United States)
Publication Date:
OSTI Identifier:
22215327
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 261; Journal Issue: 2; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANTIOXIDANTS; ARTERIOSCLEROSIS; BENZOQUINONES; DNA; ENZYMES; FLAVONOIDS; GLUTATHIONE; INDUCTION; INFLAMMATION; INHIBITION; MESSENGER-RNA; MONOCYTES; NAD; POLLUTANTS; POLYCHLORINATED BIPHENYLS

Citation Formats

Han, Sung Gu, Department of Animal and Food Sciences, College of Agriculture, University of Kentucky, Lexington, KY 40536, Han, Seong-Su, Toborek, Michal, Hennig, Bernhard, E-mail: bhennig@uky.edu, and Department of Animal and Food Sciences, College of Agriculture, University of Kentucky, Lexington, KY 40536. EGCG protects endothelial cells against PCB 126-induced inflammation through inhibition of AhR and induction of Nrf2-regulated genes. United States: N. p., 2012. Web. doi:10.1016/J.TAAP.2012.03.024.
Han, Sung Gu, Department of Animal and Food Sciences, College of Agriculture, University of Kentucky, Lexington, KY 40536, Han, Seong-Su, Toborek, Michal, Hennig, Bernhard, E-mail: bhennig@uky.edu, & Department of Animal and Food Sciences, College of Agriculture, University of Kentucky, Lexington, KY 40536. EGCG protects endothelial cells against PCB 126-induced inflammation through inhibition of AhR and induction of Nrf2-regulated genes. United States. doi:10.1016/J.TAAP.2012.03.024.
Han, Sung Gu, Department of Animal and Food Sciences, College of Agriculture, University of Kentucky, Lexington, KY 40536, Han, Seong-Su, Toborek, Michal, Hennig, Bernhard, E-mail: bhennig@uky.edu, and Department of Animal and Food Sciences, College of Agriculture, University of Kentucky, Lexington, KY 40536. Fri . "EGCG protects endothelial cells against PCB 126-induced inflammation through inhibition of AhR and induction of Nrf2-regulated genes". United States. doi:10.1016/J.TAAP.2012.03.024.
@article{osti_22215327,
title = {EGCG protects endothelial cells against PCB 126-induced inflammation through inhibition of AhR and induction of Nrf2-regulated genes},
author = {Han, Sung Gu and Department of Animal and Food Sciences, College of Agriculture, University of Kentucky, Lexington, KY 40536 and Han, Seong-Su and Toborek, Michal and Hennig, Bernhard, E-mail: bhennig@uky.edu and Department of Animal and Food Sciences, College of Agriculture, University of Kentucky, Lexington, KY 40536},
abstractNote = {Tea flavonoids such as epigallocatechin gallate (EGCG) protect against vascular diseases such as atherosclerosis via their antioxidant and anti-inflammatory functions. Persistent and widespread environmental pollutants, including polychlorinated biphenyls (PCB), can induce oxidative stress and inflammation in vascular endothelial cells. Even though PCBs are no longer produced, they are still detected in human blood and tissues and thus considered a risk for vascular dysfunction. We hypothesized that EGCG can protect endothelial cells against PCB-induced cell damage via its antioxidant and anti-inflammatory properties. To test this hypothesis, primary vascular endothelial cells were pretreated with EGCG, followed by exposure to the coplanar PCB 126. Exposure to PCB 126 significantly increased cytochrome P450 1A1 (Cyp1A1) mRNA and protein expression and superoxide production, events which were significantly attenuated following pretreatment with EGCG. Similarly, EGCG also reduced DNA binding of NF-κB and downstream expression of inflammatory markers such as monocyte chemotactic protein-1 (MCP-1) and vascular cell adhesion protein-1 (VCAM-1) after PCB exposure. Furthermore, EGCG decreased endogenous or base-line levels of Cyp1A1, MCP-1 and VCAM-1 in endothelial cells. Most of all, treatment of EGCG upregulated expression of NF-E2-related factor 2 (Nrf2)-controlled antioxidant genes, including glutathione S transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1), in a dose-dependent manner. In contrast, silencing of Nrf2 increased Cyp1A1, MCP-1 and VCAM-1 and decreased GST and NQO1 expression, respectively. These data suggest that EGCG can inhibit AhR regulated genes and induce Nrf2-regulated antioxidant enzymes, thus providing protection against PCB-induced inflammatory responses in endothelial cells. -- Highlights: ► PCBs cause endothelial inflammation and subsequent atherosclerosis. ► Nutrition can modulate toxicity by environmental pollutants. ► We demonstrated that EGCG can decrease PCB-induced inflammation. ► EGCG protection was via inhibition of AhR and induction of Nrf2 regulatory genes.},
doi = {10.1016/J.TAAP.2012.03.024},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 2,
volume = 261,
place = {United States},
year = {2012},
month = {6}
}