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(-)-Epicatechin attenuates high-glucose-induced inflammation by epigenetic modulation in human monocytes.
- Source :
-
European journal of nutrition [Eur J Nutr] 2017 Apr; Vol. 56 (3), pp. 1369-1373. Date of Electronic Publication: 2015 Dec 24. - Publication Year :
- 2017
-
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.<br />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.<br />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.<br />Conclusions: EC induces epigenetic changes and decreased NF-κB and TNF-α levels in human monocytes cultured in HG conditions such as in diabetes.
- Subjects :
- Acetylation
Cell Line
Gene Expression Regulation
Histone Acetyltransferases genetics
Histone Acetyltransferases metabolism
Histone Deacetylases genetics
Histone Deacetylases metabolism
Histones genetics
Histones metabolism
Humans
Monocytes metabolism
NF-kappa B genetics
NF-kappa B metabolism
Repressor Proteins genetics
Repressor Proteins metabolism
Tumor Necrosis Factor-alpha genetics
Tumor Necrosis Factor-alpha metabolism
Anti-Inflammatory Agents pharmacology
Catechin pharmacology
Epigenesis, Genetic
Glucose metabolism
Inflammation drug therapy
Monocytes drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1436-6215
- Volume :
- 56
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- European journal of nutrition
- Publication Type :
- Academic Journal
- Accession number :
- 26704714
- Full Text :
- https://doi.org/10.1007/s00394-015-1136-2