title: Inhibitory effects of sunitinib on ovalbumin-induced chronic experimental asthma in mice.
abstract: BACKGROUND
  Tyrosine kinase signaling cascades play a critical role in the pathogenesis of allergic airway inflammation. Sunitinib, a multitargeted receptor tyrosine kinase inhibitor, has been reported to exert potent immunoregulatory, anti-inflammatory and anti-fibrosis effects. We investigated whether sunitinib could suppress the progression of airway inflammation, airway hyperresponsiveness (AHR), and airway remodeling in a murine model of chronic asthma.
  
  
  METHODS
  Ovalbumin (OVA)-sensitized mice were chronically challenged with aerosolized OVA for 8 weeks. Some mice were intragastrically administered with sunitinib (40 mg/kg) daily during the period of OVA challenge. Twelve hours after the last OVA challenge, mice were evaluated for the development of airway inflammation, AHR and airway remodeling. The levels of total serum immunoglobulin E (IgE) and Th2 cytokines (interleukin (IL)-4 and IL-13) in bronchoalveolar lavage fluid (BALF) were measured by ELISA. The expression of phosphorylated c-kit protein in the lungs was detected by immunoprecipitation/Western blotting (IP/WB) analysis.
  
  
  RESULTS
  Sunitinib significantly inhibited eosinophilic airway inflammation, persistent AHR and airway remodeling in chronic experimental asthma. It reduced levels of total serum IgE and BALF Th2 cytokines and also lowered the expression of phosphorylated c-kit protein in remodelled airways.
  
  
  CONCLUSIONS
  Sunitinib may inhibit the development of airway inflammation, AHR and airway remodeling. It is potentially beneficial to the prevention or treatment of asthma.
authors.affiliation: Department of Respiratory Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China. hm6114@126.com
authors.forename: Mao
authors.initials: M
authors.lastname: Huang
authors.forename: Xuan
authors.initials: X
authors.lastname: Liu
authors.forename: Qiang
authors.initials: Q
authors.lastname: DU
authors.forename: Xin
authors.initials: X
authors.lastname: Yao
authors.forename: Kai-sheng
authors.initials: KS
authors.lastname: Yin
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D001249:Asthma / Q000139:chemically induced* / Q000188:drug therapy* / Q000276:immunology; D015153:Blotting, Western; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000494:pharmacology*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology*; D000077210:Sunitinib
chemical_list: D020533:Angiogenesis Inhibitors; D007211:Indoles; D018793:Interleukin-13; D011758:Pyrroles; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin; D019009:Proto-Oncogene Proteins c-kit; D000077210:Sunitinib