Peroxisome proliferator activated receptor γ modulates reactive oxygen species generation and expression of nuclear factor‐κB and hypoxia‐inducible factor‐1α in asthma

Abstract

Reactive oxygen species (ROS) play a crucial role in the pathogenesis of airway inflammation. Peroxisome proliferator activated receptor γ (PPARγ) is also involved in airway inflammation. However, the effects of PPARγ agonists on ROS generation in conditions associated with airway inflammation have not been clarified. We have used a female C57BL/6 mouse model for asthma to determine the role of PPARγ agonists and PPARγ on ROS generation. In this study, the increased ROS generation and the increased expression of T-helper type 2 cell (TH2) cytokines, adhesion molecules, chemokines, and vascular endothelial growth factor (VEGF) in lungs after ovalbumin (OVA) inhalation were significantly reduced by the administration of PPARγ agonists or adenovirus carrying PPARγ cDNA (AdPPARγ). We also showed that the increased nuclear factor-κB (NF-κB) and hypoxia-inducible factor-1α (HIF-1α) levels after OVA inhalation were decreased by the administration of them. These findings suggest that the effects of PPARγ are mediated by the modulation of ROSgeneration and expression of redox-sensitive transcription factor NF-κB and HIF-1α in asthma. This work was supported by grants from the National Research Laboratory Program and from the Medical Science and Engineering Research Center of the Korea Science and Engineering Foundation (R13-2002-038-01004-0), Republic of Korea.