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.
- oxidative stress
- peroxisome proliferator activated receptor γ
ASJC Scopus subject areas
- Immunology and Allergy