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Effect of nintedanib on airway inflammation in a mouse model of acute asthma.

Authors
  • Lee, Jongmin1
  • Rhee, Chin Kook1
  • Lee, Jong Hyuk2
  • Yoon, Hyon Jee3
  • Kim, In Kyoung1
  • Hur, Jung1
  • Kang, Ji Young1
  • Yoon, Hyoung Kyu4
  • Lee, Sook Young1
  • Kim, Young Kyoon1
  • 1 Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. , (North Korea)
  • 2 Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. , (North Korea)
  • 3 Department of Obstetrics & Gynecology, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. , (North Korea)
  • 4 Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. , (North Korea)
Type
Published Article
Journal
Journal of Asthma
Publisher
Informa UK (Taylor & Francis)
Publication Date
Jan 01, 2020
Volume
57
Issue
1
Pages
11–20
Identifiers
DOI: 10.1080/02770903.2018.1544641
PMID: 30634874
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Objective: New treatments are needed for cases of asthma that are refractory to traditional therapies. In this study, we examined the effect of oral nintedanib, an intracellular inhibitor of tyrosine kinases, on airway hyper-responsiveness (AHR) and airway smooth muscle cells, using a mouse model of experimental asthma. Methods: Asthma was experimentally induced in mice via subcutaneous injection of ovalbumin (OVA). A group of saline-injected mice served as a control group. The OVA mice were then divided into four treatment groups according to the dose of nintedanib. AHR was examined via exposure to vaporized methacholine. Airway inflammation was assessed via bronchoalveolar lavage fluid (BALF) cell counts and Th2 cytokine concentrations. Results: Baseline levels of AHR and airway inflammation were higher in OVA mice than in the control group. Treatment with nintedanib lowered AHR, BALF cell counts and BALF cytokine levels in a dose-dependent fashion. The effect of nintedanib was comparable to that of dexamethasone. In particular, treatment with nintedanib lowered the expression of transforming growth factor-β1 and inhibited the expression and phosphorylation of platelet-derived growth factor receptor-β, vascular endothelial growth factor receptor 1 (VEGFR1), VEGFR2, fibroblast growth factor receptor 2 (FGFR2), FGFR3, and extracellular signal-regulated kinase. Conclusions: Nintedanib lowered AHR and the expression of factors associated with airway inflammation and remodeling in a mouse model of experimental asthma. Our results suggest that nintedanib may be useful in the treatment of asthma.

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