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

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.