(-)-Epicatechin attenuates high-glucose-induced inflammation by epigenetic modulation in human monocytes.
Eur J Nutr
; 56(3): 1369-1373, 2017 Apr.
Article
em En
| MEDLINE
| ID: mdl-26704714
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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Monócitos
/
Catequina
/
Epigênese Genética
/
Glucose
/
Inflamação
/
Anti-Inflamatórios
Limite:
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article