Epigenetic regulation of high glucose-induced proinflammatory cytokine production in monocytes by curcumin

Jung Mi Yun, Ishwarlal Jialal, Sridevi Devaraj

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

Diabetes is a proinflammatory state. We have previously shown increased monocyte proinflammatory cytokines in patients with Type 1 and Type 2 diabetes. High glucose induces proinflammatory cytokines via epigenetic changes. Curcumin, a polyphenol responsible for the yellow color of the spice turmeric, is known to exert potent anti-inflammatory activity in vitro. Recent studies indicate that it may regulate chromatin remodeling by inhibiting histone acetylation. In this study, we aimed to test the effect of curcumin on histone acetylation and proinflammatory cytokine secretion under high-glucose conditions in human monocytes. Human monocytic (THP-1) cells were cultured in presence of mannitol (osmolar control, mannitol) or normoglycemic (NG, 5.5 mmol/L glucose) or hyperglycemic (HG, 25 mmol/L glucose) conditions in absence or presence of curcumin (1.5-12.5 μM) for 72 h. Cytokine level, nuclear factor κB (NF-κB) transactivation, histone deacetylases (HDACs) activity, histone acetylases (HATs) activity were measured by western blots, quantitative reverse transcriptase-polymerase chain reaction, enzyme-linked immunosorbent assay, immunofluorescence staining. HG significantly induced histone acetylation, NF-κB activity and proinflammatory cytokine (interleukin 6, tumor necrosis factor α and MCP-1) release from THP-1 cells. Curcumin suppressed NF-κB binding and cytokine release in THP-1 cells. Also, since p300 histone acetyltransferase is a coactivator of NF-κB, we examined its acetylation. Curcumin treatment also significantly reduced HAT activity, level of p300 and acetylated CBP/p300 gene expression, and induced HDAC2 expression by curcumin. These results indicate that curcumin decreases HG-induced cytokine production in monocytes via epigenetic changes involving NF-κB. In conclusion, curcumin supplementation by reducing vascular inflammation may prevent diabetic complications.

Original languageEnglish (US)
Pages (from-to)450-458
Number of pages9
JournalJournal of Nutritional Biochemistry
Volume22
Issue number5
DOIs
StatePublished - May 2011

Fingerprint

Curcumin
Epigenomics
Monocytes
Cytokines
Glucose
Acetylation
Histone Acetyltransferases
Histones
Mannitol
Medical problems
Curcuma
Spices
Immunosorbents
Histone Deacetylases
Chromatin Assembly and Disassembly
Polymerase chain reaction
RNA-Directed DNA Polymerase
Polyphenols
Diabetes Complications
Reverse Transcriptase Polymerase Chain Reaction

Keywords

  • Acetylation
  • Deacetylation
  • HDAC2 and NF-κB
  • P300

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

Epigenetic regulation of high glucose-induced proinflammatory cytokine production in monocytes by curcumin. / Yun, Jung Mi; Jialal, Ishwarlal; Devaraj, Sridevi.

In: Journal of Nutritional Biochemistry, Vol. 22, No. 5, 05.2011, p. 450-458.

Research output: Contribution to journalArticle

Yun, Jung Mi ; Jialal, Ishwarlal ; Devaraj, Sridevi. / Epigenetic regulation of high glucose-induced proinflammatory cytokine production in monocytes by curcumin. In: Journal of Nutritional Biochemistry. 2011 ; Vol. 22, No. 5. pp. 450-458.
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