title: Effect of intranasal rosiglitazone on airway inflammation and remodeling in a murine model of chronic asthma.
abstract: OBJECTIVE
  Asthma is characterized by airway hyperresponsiveness, inflammation, and remodeling. Peroxisome proliferator-activated receptors have been reported to regulate inflammatory responses in many cells. In this study, we examined the effects of intranasal rosiglitazone on airway remodeling in a chronic asthma model.
  
  
  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 per week for 3 months. Mice were treated intranasally with rosiglitazone with or without an antagonist during OVA challenge. We determined airway inflammation and the degree of airway remodeling by smooth muscle actin area and collagen deposition.
  
  
  RESULTS
  Mice chronically exposed to OVA developed sustained eosinophilic airway inflammation, compared with control mice. Additionally, the mice developed features of airway remodeling, including thickening of the peribronchial smooth muscle layer. Administration of rosiglitazone intranasally inhibited the eosinophilic inflammation significantly, and, importantly, airway smooth muscle remodeling in mice chronically exposed to OVA. Expression of Toll-like receptor (TLR)-4 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) was increased in the OVA group and decreased in the rosiglitazone group. Co-treatment with GW9660 (a rosiglitazone antagonist) and rosiglitazone increased the expression of TLR-4 and NF-κB.
  
  
  CONCLUSIONS
  These results suggest that intranasal administration of rosiglitazone can prevent not only air way inf lammation but also air way remodeling associated with chronic allergen challenge. This beneficial effect is mediated by inhibition of TLR-4 and NF-κB pathways.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Hwa Young
authors.initials: HY
authors.lastname: Lee
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Chin Kook
authors.initials: CK
authors.lastname: Rhee
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kang
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Chan Kwon
authors.initials: CK
authors.lastname: Park
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Sook Young
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Soon Suk
authors.initials: SS
authors.lastname: Kwon
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Young Kyoon
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Hyoung Kyu
authors.initials: HK
authors.lastname: Yoon
mesh_terms: D000199:Actins / Q000378:metabolism; D000280:Administration, Inhalation; D056151:Airway Remodeling / Q000187:drug effects*; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage*; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002908:Chronic Disease; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D010047:Ovalbumin; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced / Q000503:physiopathology; D011657:Pulmonary Eosinophilia / Q000139:chemically induced / Q000517:prevention & control; D000077154:Rosiglitazone; D015398:Signal Transduction / Q000187:drug effects; D045162:Thiazolidinediones / Q000008:administration & dosage*; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D000199:Actins; D018927:Anti-Asthmatic Agents; D016328:NF-kappa B; D047495:PPAR gamma; D045162:Thiazolidinediones; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C544013:alpha-smooth muscle actin, mouse; D000077154:Rosiglitazone; D010047:Ovalbumin; D003094:Collagen
keywords: Asthma; Remodeling; Rosiglitazone; Smooth muscle