title: Effect of peroxisome proliferator-activated receptor-gamma on airway smooth muscle thickening in a murine model of chronic asthma.
abstract: 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.
authors.affiliation: Department of Internal Medicine, College of Medicine, Catholic University of Korea, Seocho-Gu, Seoul, Korea.
authors.forename: Chin Kook
authors.initials: CK
authors.lastname: Rhee
authors.forename: Sook Young
authors.initials: SY
authors.lastname: Lee
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kang
authors.forename: Seung Joon
authors.initials: SJ
authors.lastname: Kim
authors.forename: Soon Suk
authors.initials: SS
authors.lastname: Kwon
authors.forename: Young Kyoon
authors.initials: YK
authors.lastname: Kim
authors.forename: Sung Hak
authors.initials: SH
authors.lastname: Park
mesh_terms: 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
chemical_list: 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