title: (-)-Epicatechin attenuates high-glucose-induced inflammation by epigenetic modulation in human monocytes.
abstract: OBJECTIVE
  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.
authors.affiliation: 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.
authors.forename: Isabel
authors.initials: I
authors.lastname: Cordero-Herrera
authors.affiliation: Department of Pathology & Immunology, Baylor College of Medicine and Texas Children's Hospital, 6621, Fannin Street, Houston, TX, 77030, USA.
authors.forename: Xinpu
authors.initials: X
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Sonia
authors.initials: S
authors.lastname: Ramos
authors.affiliation: Department of Pathology & Immunology, Baylor College of Medicine and Texas Children's Hospital, 6621, Fannin Street, Houston, TX, 77030, USA. devaraj@bcm.edu.
authors.forename: Sridevi
authors.initials: S
authors.lastname: Devaraj
mesh_terms: D000107:Acetylation; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002392:Catechin / Q000494:pharmacology*; D002460:Cell Line; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism*; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D006657:Histones; D016328:NF-kappa B; D012097:Repressor Proteins; D014409:Tumor Necrosis Factor-alpha; D002392:Catechin; D051548:Histone Acetyltransferases; C400300:HDAC4 protein, human; D006655:Histone Deacetylases; D005947:Glucose
keywords: Diabetes; Epicatechin; Epigenetics; Human monocytes THP-1 cells; Inflammation; Posttranslational histone modification