Isabel Cordero-Herrera1, Xinpu Chen2, Sonia Ramos1, Sridevi Devaraj3. 1. Department of Metabolism and Nutrition, Institute of Food Science and Technology and Nutrition (ICTAN), Consejo Superior de Investigaciones Científicas (CSIC), José Antonio Novais 10, Ciudad Universitaria, 28040, Madrid, Spain. 2. Department of Pathology & Immunology, Baylor College of Medicine and Texas Children's Hospital, 6621, Fannin Street, Houston, TX, 77030, USA. 3. Department of Pathology & Immunology, Baylor College of Medicine and Texas Children's Hospital, 6621, Fannin Street, Houston, TX, 77030, USA. devaraj@bcm.edu.
Abstract
PURPOSE: Diabetes is a pro-inflammatory state associated with increased monocyte activity. NF-κB is the master switch of inflammation and is activated during diabetes. (-)-Epicatechin (EC), the main cocoa flavonol, displays anti-inflammatory and anti-diabetic effects under high glucose conditions. Recently, it has been suggested that dietary polyphenols might modulate chromatin remodelling by epigenetic changes and regulate monocyte NF-κB activation and cytokine expression under diabetic conditions. The aim of the study was to test the potential anti-inflammatory role of EC via inducing posttranslational histone changes in the presence of a high glucose (HG) concentrations. METHODS: Human monocytic cells (THP-1 cells) were pre-treated with EC (5 μM) and 4 h later exposed to 25 mM glucose (HG) for a total of 24 h. Control cells were grown under normoglycemic conditions (NG, 5.5 mM glucose). Acetyl CBP/p300, HDAC4, total histone 3 (HH3), H3K9ac, H3K4me2 and H3K9me2, and phosphorylated and total levels of p65-NF-κB were analysed by Western blot. Histone acetyltransferase (HAT) activity was measured in nuclear lysates, and TNF-α release was evaluated in culture media. RESULTS: EC incubation restored to control levels (NG) the changes induced by HG in p-p65/p65-NF-ĸB ratio, acetyl CBP/p300 values and HAT activity. Moreover, EC pre-treatment counteracted the increased acetylation of H3K9 and H3K4 dimethylation and attenuated the diminished H3K9 dimethylation triggered by HG. EC also significantly decreased HG-enhanced HDAC4 levels and TNF-α release, respectively. CONCLUSIONS: EC induces epigenetic changes and decreased NF-κB and TNF-α levels in human monocytes cultured in HG conditions such as in diabetes.
PURPOSE:Diabetes is a pro-inflammatory state associated with increased monocyte activity. NF-κB is the master switch of inflammation and is activated during diabetes. (-)-Epicatechin (EC), the main cocoaflavonol, displays anti-inflammatory and anti-diabetic effects under high glucose conditions. Recently, it has been suggested that dietary polyphenols might modulate chromatin remodelling by epigenetic changes and regulate monocyte NF-κB activation and cytokine expression under diabetic conditions. The aim of the study was to test the potential anti-inflammatory role of EC via inducing posttranslational histone changes in the presence of a high glucose (HG) concentrations. METHODS:Human monocytic cells (THP-1 cells) were pre-treated with EC (5 μM) and 4 h later exposed to 25 mM glucose (HG) for a total of 24 h. Control cells were grown under normoglycemic conditions (NG, 5.5 mM glucose). Acetyl CBP/p300, HDAC4, total histone 3 (HH3), H3K9ac, H3K4me2 and H3K9me2, and phosphorylated and total levels of p65-NF-κB were analysed by Western blot. Histone acetyltransferase (HAT) activity was measured in nuclear lysates, and TNF-α release was evaluated in culture media. RESULTS:EC incubation restored to control levels (NG) the changes induced by HG in p-p65/p65-NF-ĸB ratio, acetyl CBP/p300 values and HAT activity. Moreover, EC pre-treatment counteracted the increased acetylation of H3K9 and H3K4 dimethylation and attenuated the diminished H3K9 dimethylation triggered by HG. EC also significantly decreased HG-enhanced HDAC4 levels and TNF-α release, respectively. CONCLUSIONS:EC induces epigenetic changes and decreased NF-κB and TNF-α levels in human monocytes cultured in HG conditions such as in diabetes.
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