Peroxisome proliferator activated receptor-γ modulates reactive oxygen species generation and activation of nuclear factor-κB and hypoxia-inducible factor 1α in allergic airway disease of mice

Kyung Sun Lee, So Ri Kim, Seoung Ju Park, Hee Sun Park, Kyung Hoon Min, Sun Mi Jin, Moon Kyu Lee, Uh Hyun Kim, Yong Chul Lee

Research output: Contribution to journalArticlepeer-review

89 Citations (Scopus)

Abstract

Background: Reactive oxygen species (ROSs) play a crucial role in the pathogenesis of airway inflammation. Peroxisome proliferator activated receptor (PPAR)-γ is also involved in airway inflammation. We have demonstrated that the administration of PPARγ agonists or adenovirus carrying PPARγ cDNA (AdPPARγ) reduced bronchial inflammation and airway hyperresponsiveness. However, the effects of PPARγ on ROS generation in conditions associated with airway inflammation have not been clarified. Objective: This study aimed to investigate the effects of the PPARγ on ROS generation in allergic airway disease of mice. Methods: We have used a female C57BL/6 mouse model for allergic airway disease to determine the role of PPARγ. Results: In this study with an ovalbumin-induced murine model of allergic airway disease, the increased ROS generation and the increased expression of TH2 cell cytokines, adhesion molecules, chemokines, and vascular endothelial growth factor in lungs after ovalbumin inhalation were significantly reduced by the administration of PPARγ agonists or AdPPARγ. We also showed that the increased nuclear factor-κB and hypoxia-inducible factor 1α levels in nuclear protein extracts of lung tissues after ovalbumin inhalation were decreased by the administration of PPARγ agonists or AdPPARγ. Conclusion: These results indicate that the effects of PPARγ are mediated by the modulation of ROS generation and activation of redox-sensitive transcription factor nuclear factor-κB and HIF-1α in allergic airway disease of mice. Clinical implications: Thus, these findings provide a pivotal molecular mechanism for the use of PPARγ agonists to prevent and/or treat asthma and other airway inflammatory disorders.

Original languageEnglish
Pages (from-to)120-127
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume118
Issue number1
DOIs
Publication statusPublished - 2006 Jul
Externally publishedYes

Keywords

  • Asthma
  • HIF-1α
  • NF-κB
  • oxidative stress
  • peroxisome proliferator activated receptor γ

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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