EGCG prevents PCB-126-induced endothelial cell inflammation via epigenetic modifications of NF-κB target genes in human endothelial cells

Abstract

Anti-inflammatory polyphenols, such as epigallocatechin-3-gallate (EGCG), have been shown to protect against the toxicity of environmental pollutants. It is well known that bioactive food compounds such as polyphenols may exert their protection by modulating inflammatory pathways regulated through nuclear factor-kappa B (NF-κB) signaling. EGCG has been reported to inhibit NF-κB activation. We hypothesize that EGCG can protect against PCB-induced endothelial inflammation in part through epigenetic regulation of NF-kB-regulated inflammatory genes. In order to test this hypothesis, human endothelial cells (EA.hy926) were exposed to physiologically relevant levels of coplanar PCB 126 and/or 15 or 30 μM of EGCG, followed by quantification of NF-kB subunit p65, histone acetyltransferase (HAT) p300 and histone deacetylases (HDACs) accumulation through ChIP assay in the promotor region of inflammatory genes. In addition, the enrichment of the acetylated H3 (ac-H3) was also quantified. PCB 126 exposure increased the expression of vascular inflammatory mediators, including interleukin (IL)-6, C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and IL-1α/β, which were prevented by pre-treatment with EGCG. This inhibitory effect by EGCG correlated with abolished nuclear import of p65, decreased chromatin binding of p65 and p300, as well as increased chromatin binding of HDAC1/2. Furthermore, EGCG induced hypo-acetylation of H3, which accounts for deactivation of downstream genes. These data suggest that EGCG-induced epigenetic modifications can decrease PCB-induced vascular toxicity.

Neuroprotective effect of (‑)‑epigallocatechin‑3‑gallate on autoimmune thyroiditis in a rat model by an anti‑inflammation effect, anti‑apoptosis and inhibition of TRAIL signaling pathway

“…In the present study, treatment with EGCG significantly inhibited the AIT-induced urinary iodine values, the relative thyroid weight and the thyroid pathological features in the AIT rats, while it suppressed IL-1β, IFN-γ and TNF-α levels, as well as NF-κB protein expression, which showed that EGCG had a neuroprotective effect against AIT (16). These results are in accordance with the findings of Liu et al, which suggested that EGCG prevents PCB-126-induced endothelial cell inflammation through the inhibition of NF-κB in human endothelial cells (12).…”

An Update on the Health Benefits of Green Tea

“…Studies have shown that green tea catechins cause a reduction in the number of leukocyte-endothelial cell adhesion molecules (CAMs), such as ICAM-1, VCAM-1, and E-selection, expressed on the endothelial cell surface. This restricts the ability of the neutrophils to migrate to sites of infection [71,72]. Other studies have shown that factors known to regulate neutrophil function, such as IL-1β, IL-2, TNF-α, and granulocyte-macrophage colony-stimulating factor (GM-CSF), are suppressed by consumption of green tea or EGCG, resulting in inhibition of inflammation [73][74][75].…”

The role of nutrition in influencing mechanisms involved in environmentally mediated diseases

“…This may account for the observed up-regulation of p65 and associated inflammatory genes. These data suggest that dioxin-like PCBs may exert endothelial cell toxicity through changes in histone modifications (67, 68). …”

“…Epigenetic modifications of DNA and histones alter cellular phenotypes without changing genetic codes. A recent study demonstrated that endothelial cell dysfunction induced by exposure to dioxin-like PCBs is mediated in part through histone modifications (68). Increased accumulation of the histone demethylase JMJD2B in the p65 promoter of NF-κB led to a depletion of H3K9me3 repression marks (67).…”

“…Additionally, poly-phenols and omega-3 PUFAs have been shown to decrease toxicant-induced maladies including liver diseases, tumor formation and growth and endothelial cell activation (63). Most importantly, plant-derived flavonoids such as epigallocatechin-3-gallate (EGCG), can decrease oxidative stress and inflammation, and this observed protection may be in part controlled via epigenetic mechanisms (68). Understanding of the epigenetic control mechanisms of pollutant-induced diseases will allow for more focused therapeutic and preventative measures which can be implemented during developmental or early phases in life and thus may be highly applicable to the fields of public health and risk assessment.…”