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The human myeloperoxidase gene is regulated by LXR and PPARalpha ligands

Wanda F Reynolds1, Alan P Kumar, F Javier Piedrafita

  • 1Sidney Kimmel Cancer Center, San Diego, CA 92121, USA. wreynolds@skcc.org

Biochemical and Biophysical Research Communications
|September 8, 2006
PubMed

Insights

Liver X Receptor (LXR) and Peroxisome proliferator-activated receptor alpha (PPARα) ligands regulate human myeloperoxidase (MPO) expression. These nuclear receptors target the MPO gene, impacting inflammatory processes in macrophages.

Area of Science:

  • Molecular biology
  • Cell biology
  • Biochemistry

Background:

  • Myeloperoxidase (MPO) is an enzyme in macrophages linked to atherosclerosis and cholesterol metabolism.
  • Liver X Receptor alpha (LXRα) and Peroxisome proliferator-activated receptor alpha (PPARα) are key regulators of cholesterol and inflammation in macrophages.

Purpose of the Study:

  • To investigate the impact of LXR and PPARα ligands on human MPO gene expression.
  • To determine the regulatory mechanisms of MPO by these nuclear receptors.

Main Methods:

  • Analysis of MPO promoter activity using Alu receptor response elements (AluRRE).
  • Treatment of primary human macrophages and transgenic mouse models with LXR and PPARα ligands.
  • Quantitative assessment of MPO mRNA expression.

Main Results:

  • LXR and PPARα, as heterodimers with RXR, bind to overlapping sites in the MPO promoter's AluRRE.
  • LXR ligand T0901317 suppressed MPO mRNA in human and mouse macrophages.
  • PPARα ligand GW9578 differentially regulated MPO expression based on macrophage type (GM-CSF vs. M-CSF).
  • The mouse MPO gene, lacking AluRRE, was not affected by LXR or PPARα ligands.

Conclusions:

  • Human MPO is identified as a novel target gene for LXR and PPARα.
  • These findings highlight the role of LXR and PPARα in controlling proinflammatory gene expression in macrophages.
  • The primate-specific AluRRE is crucial for MPO regulation by LXR and PPARα.

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