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.
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.
Lee
Kyung Sun
KS
Department of Internal Medicine, Chonbuk National University Medical School, San 2-20, Geumam-dong, Jeonju 561-180, Korea.
Kim
So Ri
SR
Park
Seoung Ju
SJ
Park
Hee Sun
HS
Min
Kyung Hoon
KH
Jin
Sun Mi
SM
Lee
Moon Kyu
MK
Kim
Uh Hyun
UH
Lee
Yong Chul
YC
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
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