Activation of farnesoid X receptor downregulates monocyte chemoattractant protein-1 in murine macrophage

Biochem Biophys Res Commun. 2015 Nov 27;467(4):841-6. doi: 10.1016/j.bbrc.2015.10.056. Epub 2015 Oct 22.

Abstract

Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily, which plays important roles in bile acids/lipid homeostasis and inflammation. Monocyte chemoattractant protein-1 (MCP-1) contributes to macrophage infiltration into body tissues during inflammation. Here we investigated whether FXR can regulate MCP-1 expression in murine macrophage. FXR activation down regulate MCP-1 mRNA and protein levels in ANA-1 and Raw264.7 cells. Luciferase reporter assay, Gel shift and Chromatin immunoprecipitation assays have revealed that the activated FXR bind to the FXR element located in -738 bp ∼ -723 bp in MCP-1 promoter. These results suggested that FXR may serve as a novel target for regulating MCP-1 levels for the inflammation related diseases therapies.

Keywords: Bile acids; Farnesoid X receptor; Inflammation; Macrophage; Monocyte chemoattractant protein-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Cell Line / drug effects
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism*
  • Chenodeoxycholic Acid / pharmacology
  • Down-Regulation
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Mice
  • Promoter Regions, Genetic
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*

Substances

  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Receptors, Cytoplasmic and Nuclear
  • farnesoid X-activated receptor
  • Chenodeoxycholic Acid