The Korean journal of internal medicine

The Korean Association of Internal Medicine (대한내과학회)
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Different anti-remodeling effect of nilotinib and fluticasone in a chronic asthma model

  • Kang, Hye Seon (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) ;
  • Rhee, Chin Kook (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) ;
  • Lee, Hea Yon (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) ;
  • Yoon, Hyoung Kyu (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) ;
  • Kwon, Soon Seok (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) ;
  • Lee, Sook Young (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)
  • Received : 2015.01.04
  • Accepted : 2015.08.16
  • Published : 2016.11.01
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Abstract

Background/Aims: 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 f luticasone 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 ${\beta}1$ 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.

Keywords

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