EGCG protects endothelial cells against PCB 126-induced inflammation through inhibition of AhR and induction of Nrf2-regulated genes
- PMID: 22521609
- PMCID: PMC3358429
- DOI: 10.1016/j.taap.2012.03.024
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. 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.
Copyright © 2012 Elsevier Inc. All rights reserved.
Conflict of interest statement
The authors declare no conflict of interest.
Figures
![Figure 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3358429/bin/nihms369113f1.gif)
![Figure 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3358429/bin/nihms369113f2.gif)
![Figure 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3358429/bin/nihms369113f3.gif)
![Figure 4](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3358429/bin/nihms369113f4.gif)
![Figure 5](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3358429/bin/nihms369113f5.gif)
![Figure 6](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3358429/bin/nihms369113f6.gif)
Similar articles
-
Protective Effect of Epigallocatechin Gallate on Endothelial Disorders in Atherosclerosis.J Cardiovasc Pharmacol. 2020 Apr;75(4):292-298. doi: 10.1097/FJC.0000000000000792. J Cardiovasc Pharmacol. 2020. PMID: 31895874 Review.
-
EGCG prevents PCB-126-induced endothelial cell inflammation via epigenetic modifications of NF-κB target genes in human endothelial cells.J Nutr Biochem. 2016 Feb;28:164-70. doi: 10.1016/j.jnutbio.2015.10.003. Epub 2015 Oct 26. J Nutr Biochem. 2016. PMID: 26878794 Free PMC article.
-
The pathological roles of environmental and redox stresses in cardiovascular diseases.Environ Health Prev Med. 2013 May;18(3):177-84. doi: 10.1007/s12199-012-0326-2. Epub 2012 Dec 29. Environ Health Prev Med. 2013. PMID: 23275240 Free PMC article. Review.
-
Dietary flavonoids modulate PCB-induced oxidative stress, CYP1A1 induction, and AhR-DNA binding activity in vascular endothelial cells.Toxicol Sci. 2003 Nov;76(1):212-9. doi: 10.1093/toxsci/kfg227. Epub 2003 Sep 11. Toxicol Sci. 2003. PMID: 12970578
-
Proinflammatory properties of coplanar PCBs: in vitro and in vivo evidence.Toxicol Appl Pharmacol. 2002 Jun 15;181(3):174-83. doi: 10.1006/taap.2002.9408. Toxicol Appl Pharmacol. 2002. PMID: 12079426
Cited by
-
Potential Role of Dietary Phenolic Compounds in the Prevention and Treatment of Rheumatoid Arthritis: Current Reports.Pharmaceuticals (Basel). 2024 May 6;17(5):590. doi: 10.3390/ph17050590. Pharmaceuticals (Basel). 2024. PMID: 38794160 Free PMC article. Review.
-
Polyphenols: immunonutrients tipping the balance of immunometabolism in chronic diseases.Front Immunol. 2024 Mar 15;15:1360065. doi: 10.3389/fimmu.2024.1360065. eCollection 2024. Front Immunol. 2024. PMID: 38558823 Free PMC article. Review.
-
Combined effects of green tea supplementation and eccentric exercise on nuclear factor erythroid 2-related factor 2 activity.Eur J Appl Physiol. 2024 Jan;124(1):245-256. doi: 10.1007/s00421-023-05271-8. Epub 2023 Jul 13. Eur J Appl Physiol. 2024. PMID: 37439906 Free PMC article.
-
Network medicine framework shows that proximity of polyphenol targets and disease proteins predicts therapeutic effects of polyphenols.Nat Food. 2021 Mar;2(3):143-155. doi: 10.1038/s43016-021-00243-7. Epub 2021 Mar 19. Nat Food. 2021. PMID: 37117448
-
Catechins: Protective mechanism of antioxidant stress in atherosclerosis.Front Pharmacol. 2023 Mar 24;14:1144878. doi: 10.3389/fphar.2023.1144878. eCollection 2023. Front Pharmacol. 2023. PMID: 37033663 Free PMC article. Review.
References
-
- Badimon L, Storey RF, Vilahur G. Update on lipids, inflammation and atherothrombosis. Thromb Haemost. 2011 - PubMed
-
- Crespo I, Garcia-Mediavilla MV, Gutierrez B, Sanchez-Campos S, Tunon MJ, Gonzalez-Gallego J. A comparison of the effects of kaempferol and quercetin on cytokine-induced pro-inflammatory status of cultured human endothelial cells. Br J Nutr. 2008;100:968–976. - PubMed
-
- Everett CJ, Mainous AG, 3rd, Frithsen IL, Player MS, Matheson EM. Association of polychlorinated biphenyls with hypertension in the 1999–2002 National Health and Nutrition Examination Survey. Environ Res. 2008;108:94–97. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous