Peroxisome proliferator-activated receptors alpha and gamma down-regulate allergic inflammation and eosinophil activation

J Exp Med. 2003 Aug 4;198(3):411-21. doi: 10.1084/jem.20021384.

Abstract

Allergic asthma is characterized by airway hyperresponsiveness, eosinophilia, and mucus accumulation and is associated with increased IgE concentrations. We demonstrate here that peroxisome proliferator-activated receptors (PPARs), PPAR-alpha and PPAR-gamma, which have been shown recently to be involved in the regulation of various cell types within the immune system, decrease antigen-induced airway hyperresponsiveness, lung inflammation, eosinophilia, cytokine production, and GATA-3 expression as well as serum levels of antigen-specific IgE in a murine model of human asthma. In addition, we demonstrate that PPAR-alpha and -gamma are expressed in eosinophils and their activation inhibits in vitro chemotaxis and antibody-dependent cellular cytotoxicity. Thus, PPAR-alpha and -gamma (co)agonists might be of therapeutic interest for the regulation of allergic or inflammatory reactions by targeting both regulatory and effector cells involved in the immune response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anilides / metabolism
  • Animals
  • Asthma / immunology*
  • Chemotaxis / physiology
  • DNA-Binding Proteins / metabolism
  • Disease Models, Animal
  • Down-Regulation*
  • Eosinophils / immunology*
  • Eosinophils / metabolism
  • GATA3 Transcription Factor
  • Humans
  • Inflammation / immunology
  • Lung / metabolism
  • Lung / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Rats
  • Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / immunology*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Respiratory Hypersensitivity / immunology*
  • Rosiglitazone
  • Thiazoles / metabolism
  • Thiazolidinediones*
  • Trans-Activators / metabolism
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / genetics
  • Transcription Factors / immunology*
  • Transcription Factors / metabolism

Substances

  • 2-chloro-5-nitrobenzanilide
  • Anilides
  • DNA-Binding Proteins
  • GATA3 Transcription Factor
  • GATA3 protein, human
  • Gata3 protein, mouse
  • Receptors, Cytoplasmic and Nuclear
  • Thiazoles
  • Thiazolidinediones
  • Trans-Activators
  • Transcription Factors
  • Rosiglitazone
  • ciglitazone