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http://dx.doi.org/10.3904/kjim.2015.002

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)
Publication Information
The Korean journal of internal medicine / v.31, no.6, 2016 , pp. 1150-1158 More about this Journal
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
Asthm; Nilotinib; Fluticasone; Airway remodeling;
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