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.
Published by Elsevier Ltd.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Acetylation / drug effects
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Animals
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Curcumin / pharmacology*
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Epigenesis, Genetic / drug effects*
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Histones / metabolism
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Lipopolysaccharides / pharmacology*
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Lung / drug effects
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Lung / metabolism
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Lung / pathology
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Macrophages / drug effects
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Macrophages / metabolism
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Male
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Membrane Glycoproteins / genetics*
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Membrane Glycoproteins / metabolism
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Methylation / drug effects
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Mice
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Mice, Inbred C57BL
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Promoter Regions, Genetic / genetics
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Protein Binding / drug effects
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Proto-Oncogene Proteins / metabolism
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Reactive Oxygen Species / metabolism
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Receptors, Immunologic / genetics*
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Receptors, Immunologic / metabolism
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Sepsis / genetics
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Sepsis / pathology
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Survival Analysis
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Trans-Activators / metabolism
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Transcription Factor RelA / metabolism
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Triggering Receptor Expressed on Myeloid Cells-1
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p300-CBP Transcription Factors / metabolism
Substances
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Histones
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Lipopolysaccharides
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Membrane Glycoproteins
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Proto-Oncogene Proteins
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Reactive Oxygen Species
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Receptors, Immunologic
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TREM1 protein, mouse
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Trans-Activators
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Transcription Factor RelA
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Triggering Receptor Expressed on Myeloid Cells-1
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proto-oncogene protein Spi-1
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p300-CBP Transcription Factors
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p300-CBP-associated factor
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Curcumin