Effect of peroxisome proliferator-activated receptor-gamma on airway smooth muscle thickening in a murine model of chronic asthma.
BACKGROUND
Asthma is characterized by airway hyperresponsiveness (AHR), inflammation and remodeling. Peroxisome proliferator-activated receptors (PPARs) were reported to regulate inflammatory responses in many cells. In this study we examined the effect of a PPAR-gamma agonist on the airway smooth muscle and the production of transforming growth factor (TGF)-beta1 and vascular endothelial growth factor (VEGF).


METHODS
We developed a mouse model of airway remodeling including smooth muscle thickening in which ovalbumin (OVA)-sensitized mice were repeatedly exposed to intranasal OVA administration twice a week for 3 months. Mice were treated intranasally with ciglitazone during OVA challenge.


RESULTS
Mice chronically exposed to OVA developed sustained eosinophilic airway inflammation and AHR to methacholine compared with control mice. In addition, the mice chronically exposed to OVA developed features of airway remodeling, including thickening of the peribronchial smooth muscle layer. Administration of ciglitazone intranasally significantly inhibited the development of AHR, eosinophilic inflammation, and importantly, airway smooth muscle remodeling in mice chronically exposed to OVA. However, intranasal ciglitazone treatment did not reduce the level of TGF-beta1 and VEGF in bronchoalveolar lavage fluid.


CONCLUSIONS
These results suggest that intranasal administration of ciglitazone can prevent not only airway inflammation, but also airway remodeling associated with chronic allergen challenge. The mechanism might not be related to VEGF and TGF production. Further study is needed.
Rhee
Chin Kook
CK
Department of Internal Medicine, College of Medicine, Catholic University of Korea, Seocho-Gu, Seoul, Korea.
Lee
Sook Young
SY
Kang
Ji Young
JY
Kim
Seung Joon
SJ
Kwon
Soon Suk
SS
Kim
Young Kyoon
YK
Park
Sung Hak
SH
D000281:Administration, Intranasal; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D001980:Bronchi / Q000187:drug effects / Q000473:pathology*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D004195:Disease Models, Animal; D004804:Eosinophils / Q000166:cytology; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D009130:Muscle, Smooth / Q000187:drug effects / Q000473:pathology*; D010047:Ovalbumin / Q000276:immunology; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism*; D012130:Respiratory Hypersensitivity / Q000188:drug therapy / Q000503:physiopathology; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D053773:Transforming Growth Factor beta1 / Q000032:analysis / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000378:metabolism
D018927:Anti-Asthmatic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D010047:Ovalbumin; C039671:ciglitazone