Peroxisome proliferator-activated receptor γ ligands attenuate immunological symptoms of experimental allergic asthma

  • Mueller C
  • Weaver V
  • Vanden Heuvel J
 et al. 
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Abstract

Asthma is characterized by a predominant TH2 type immune response to airborne allergens. Controlling TH2 cell function has been proposed as therapy for this disease. We show here that ligands for the nuclear receptor peroxisome proliferator activated receptor (PPAR)γ significantly reduced the immunological symptoms of allergic asthma in a murine model of this disease. A PPARγ ligand, 15-deoxy-delta(12,14) -prostaglandin J(2), significantly inhibited production of the TH2 type cytokine IL-5 from T cells activated in vitro. More importantly, in a murine model of allergic asthma, mice treated orally with ciglitazone, a potent synthetic PPARγ ligand, had significantly reduced lung inflammation and mucous production following induction of allergic asthma. T cells from these ciglitazone treated mice also produced less IFNγ, IL-4, and IL-2 upon rechallenge in vitro with the model allergen. Our results suggest that ligands for PPARγ may be effective treatments for asthmatic patients. © 2003 Elsevier Inc. All rights reserved.

Author-supplied keywords

  • Allergy
  • Asthma
  • Lung
  • PPAR
  • T lymphocytes
  • Transcription factors

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