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Induction of CXCR2 receptor by peroxisome proliferator-activated receptor gamma in human macrophages

Elena Rigamonti1, Coralie Fontaine, Bruno Lefebvre

  • 1Institut Pasteur de Lille, France.

Arteriosclerosis, Thrombosis, and Vascular Biology
|February 23, 2008
PubMed
Abstract

Insights

Peroxisome proliferator-activated receptor (PPAR) gamma enhances immune responses by increasing CXCR2 expression in human macrophages. This mechanism boosts macrophage responsiveness to CXC chemokines, aiding in host defense against pathogens.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Macrophages are key immune cells involved in host defense.
  • Interleukin-8 (IL-8) and CXC chemokines, acting via CXCR1/CXCR2, recruit and activate phagocytes.
  • Peroxisome proliferator-activated receptor (PPAR) gamma has known anti-inflammatory effects in macrophages.

Purpose of the Study:

  • To investigate the role of PPAR-gamma in regulating the CXC chemokine pathway in human macrophages.
  • To determine if PPAR-gamma influences the expression of CXCR1 and CXCR2 receptors.

Main Methods:

  • Primary human macrophages were treated with synthetic PPAR-gamma ligands in vitro.
  • Experiments were conducted in atherosclerotic plaques in vivo.
  • Gene expression, protein levels, promoter activity (EMSA, ChIP, transfection), and cellular response (superoxide anion production) were analyzed.

Main Results:

  • PPAR-gamma ligands increased CXCR2 gene and protein expression in a PPAR-gamma-dependent manner.
  • PPAR-gamma was shown to directly activate the CXCR2 promoter via a PPRE.
  • Macrophages exhibited enhanced responsiveness to CXCR2 ligands following PPAR-gamma-induced CXCR2 expression.

Conclusions:

  • PPAR-gamma upregulates CXCR2 expression in human macrophages.
  • This represents a novel mechanism by which PPAR-gamma can augment the immune response.
  • PPAR-gamma activation enhances macrophage effector functions through the CXC chemokine pathway.

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