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Peroxisome proliferator-activated receptor-gamma is a new therapeutic target in sepsis and inflammation

Basilia Zingarelli1, James A Cook

  • 1Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center and the College of Medicine, University of Cincinnati, Cincinnati, Ohio 45229, USA. basilia.zingarelli@cchmc.org

Shock (Augusta, Ga.)
|April 19, 2005
PubMed

Insights

Peroxisome proliferator-activated receptor-gamma (PPARgamma) ligands, like thiazolidinediones, show anti-inflammatory effects. These compounds offer potential therapeutic uses beyond diabetes for conditions such as sepsis and reperfusion injury.

Area of Science:

  • Molecular Biology
  • Endocrinology
  • Pharmacology

Background:

  • Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a nuclear receptor regulating lipid metabolism, inflammation, and cell proliferation.
  • PPARgamma forms heterodimers with retinoid X receptor, binding DNA to modulate gene transcription upon ligand activation.
  • Thiazolidinediones are synthetic PPARgamma agonists used to study its gene regulation.

Purpose of the Study:

  • To provide an overview of PPARgamma's role in inflammatory response regulation.
  • To highlight the therapeutic potential of PPARgamma ligands beyond diabetes treatment.

Main Methods:

  • Review of in vitro and in vivo studies on PPARgamma activation.
  • Characterization of genes regulated by PPARgamma using thiazolidinediones.
  • Identification of natural ligands like J2 series cyclopentenone prostaglandins.

Main Results:

  • Pharmacological activation of PPARgamma by 15-deoxy-Delta(12,14)-PGJ2 or thiazolidinediones demonstrates anti-inflammatory effects.
  • PPARgamma plays a key role in modulating inflammatory pathways.
  • Synthetic and natural ligands effectively activate PPARgamma.

Conclusions:

  • PPARgamma ligands exhibit significant anti-inflammatory properties.
  • PPARgamma agonists represent promising therapeutic strategies for inflammatory diseases.
  • Potential applications include sepsis, inflammation, and reperfusion injury beyond glycemic control.

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