Curcumin mediated epigenetic modulation inhibits TREM-1 expression in response to lipopolysaccharide

Zhihong Yuan, Mansoor Ali Syed, Dipti Panchal, Daniel Rogers, Myungsoo Joo, Ruxana T. Sadikot

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Triggering receptor expressed on myeloid cells 1 (TREM-1) is a member of the immunoglobulin superfamily expressed on macrophage and neutrophils and is emerging as a potent amplifier of TLR initiated inflammatory responses. Blockade of TREM-1 improves survival in animal models of sepsis. In this study, we show that curcumin or diferuloylmethane, a yellow pigment present in turmeric, a major ingredient of curry spice inhibited the expression of TREM-1 in vitro in primary bone marrow derived macrophages and in vivo in lungs of mice with sepsis. Chromatin immunoprecipitation assay confirmed that curcumin inhibits the binding of p65 to TREM-1 promoter in response to LPS. Further we show that curcumin inhibited p300 activity in the TREM-1 promoter region leading to hypoacetylation of histone 3 and 4 in the lysine residues. Inhibition of TREM-1 by curcumin is oxidant independent. These studies are the first report to define a detailed molecular mechanism by which curcumin exerts anti-inflammatory effects through regulation of TREM-1 gene activity and provide additional mechanistic insights into the anti-inflammatory effect of curcumin.

Original languageEnglish (US)
Pages (from-to)2032-2043
Number of pages12
JournalInternational Journal of Biochemistry and Cell Biology
Volume44
Issue number11
DOIs
StatePublished - Nov 2012
Externally publishedYes

Keywords

  • Curcumin
  • Epigenetic
  • Sepsis
  • TREM-1

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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