title: Peroxisome proliferator activated receptor-gamma modulates reactive oxygen species generation and activation of nuclear factor-kappaB and hypoxia-inducible factor 1alpha in allergic airway disease of mice.
abstract: BACKGROUND
  Reactive oxygen species (ROSs) play a crucial role in the pathogenesis of airway inflammation. Peroxisome proliferator activated receptor (PPAR)-gamma is also involved in airway inflammation. We have demonstrated that the administration of PPARgamma agonists or adenovirus carrying PPARgamma cDNA (AdPPARgamma) reduced bronchial inflammation and airway hyperresponsiveness. However, the effects of PPARgamma on ROS generation in conditions associated with airway inflammation have not been clarified.
  
  
  OBJECTIVE
  This study aimed to investigate the effects of the PPARgamma 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 PPARgamma.
  
  
  RESULTS
  In this study with an ovalbumin-induced murine model of allergic airway disease, the increased ROS generation and the increased expression of T(H)2 cell cytokines, adhesion molecules, chemokines, and vascular endothelial growth factor in lungs after ovalbumin inhalation were significantly reduced by the administration of PPARgamma agonists or AdPPARgamma. We also showed that the increased nuclear factor-kappaB and hypoxia-inducible factor 1alpha levels in nuclear protein extracts of lung tissues after ovalbumin inhalation were decreased by the administration of PPARgamma agonists or AdPPARgamma.
  
  
  CONCLUSIONS
  These results indicate that the effects of PPARgamma are mediated by the modulation of ROS generation and activation of redox-sensitive transcription factor nuclear factor-kappaB and HIF-1alpha in allergic airway disease of mice.
  
  
  CONCLUSIONS
  Thus, these findings provide a pivotal molecular mechanism for the use of PPARgamma agonists to prevent and/or treat asthma and other airway inflammatory disorders.
authors.affiliation: Department of Internal Medicine, Chonbuk National University Medical School, San 2-20, Geumam-dong, Jeonju 561-180, Korea.
authors.forename: Kyung Sun
authors.initials: KS
authors.lastname: Lee
authors.forename: So Ri
authors.initials: SR
authors.lastname: Kim
authors.forename: Seoung Ju
authors.initials: SJ
authors.lastname: Park
authors.forename: Hee Sun
authors.initials: HS
authors.lastname: Park
authors.forename: Kyung Hoon
authors.initials: KH
authors.lastname: Min
authors.forename: Sun Mi
authors.initials: SM
authors.lastname: Jin
authors.forename: Moon Kyu
authors.initials: MK
authors.lastname: Lee
authors.forename: Uh Hyun
authors.initials: UH
authors.lastname: Kim
authors.forename: Yong Chul
authors.initials: YC
authors.lastname: Lee
mesh_terms: D000813:Anilides / Q000494:pharmacology; D000818:Animals; D001249:Asthma / Q000378:metabolism*; D018946:Chemokine CCL5 / Q000032:analysis; D005260:Female; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D047495:PPAR gamma / Q000502:physiology*; D000077205:Pioglitazone; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D018946:Chemokine CCL5; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016328:NF-kappa B; D047495:PPAR gamma; D017382:Reactive Oxygen Species; D045162:Thiazolidinediones; D019010:Vascular Cell Adhesion Molecule-1; D000077154:Rosiglitazone; D018799:Intercellular Adhesion Molecule-1; D000077205:Pioglitazone