title: Different anti-remodeling effect of nilotinib and fluticasone in a chronic asthma model.
abstract: OBJECTIVE
  Inhaled corticosteroids are the most effective treatment currently available for asthma, but their beneficial effect against airway remodeling is limited. The tyrosine kinase inhibitor nilotinib has inhibitory activity against c-kit and the platelet-derived growth factor receptor. We compared the effects of fluticasone and nilotinib on airway remodeling in a chronic asthma model. We also examined whether co-treatment with nilotinib and fluticasone had any synergistic effect in preventing airway remodeling.
  
  
  METHODS
  We developed a mouse model of airway remodeling, including smooth muscle thickening, in which ovalbumin (OVA)-sensitized female BALB/c-mice were repeatedly exposed to intranasal OVA administration twice per week for 3 months. Mice were treated with fluticasone and/or nilotinib intranasally during the OVA challenge.
  
  
  RESULTS
  Mice chronically exposed to OVA developed eosinophilic airway inflammation and showed features of airway remodeling, including thickening of the peribronchial smooth muscle layer. Both fluticasone and nilotinib attenuated airway smooth muscle thickening. However, only nilotinib suppressed fibrotic changes, demonstrating inhibition of collagen deposition. Fluticasone reduced pro-inflammatory cells, such as eosinophils, and several cytokines, such as interleukin 4 (IL-4), IL-5, and IL-13, induced by repeated OVA challenges. On the other hand, nilotinib reduced transforming growth factor β1 levels in bronchoalveolar lavage fluid and inhibited fibroblast proliferation significantly.
  
  
  CONCLUSIONS
  These results suggest that fluticasone and nilotinib suppressed airway remodeling in this chronic asthma model through anti-inflammatory and anti-fibrotic pathways, respectively.
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Hye Seon
authors.initials: HS
authors.lastname: Kang
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Chin Kook
authors.initials: CK
authors.lastname: Rhee
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Hea Yon
authors.initials: HY
authors.lastname: Lee
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Yeouido St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Hyoung Kyu
authors.initials: HK
authors.lastname: Yoon
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Bucheon St. Mary's Hospital, The Catholic University of Korea, Bucheon, Korea.
authors.forename: Soon Seok
authors.initials: SS
authors.lastname: Kwon
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Sook Young
authors.initials: SY
authors.lastname: Lee
mesh_terms: D000281:Administration, Intranasal; D056151:Airway Remodeling / Q000187:drug effects*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002908:Chronic Disease; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D000068298:Fluticasone / Q000008:administration & dosage*; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008807:Mice, Inbred BALB C; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D010047:Ovalbumin; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011658:Pulmonary Fibrosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011743:Pyrimidines / Q000008:administration & dosage*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D016207:Cytokines; D018836:Inflammation Mediators; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1; D010047:Ovalbumin; D003094:Collagen; D000068298:Fluticasone; C498826:nilotinib
keywords: Airway remodeling; Asthm; Fluticasone; Nilotinib