Inhibitory effects of sunitinib on ovalbumin-induced chronic experimental asthma in mice

• Published in: Chinese medical journal 2009-05, Vol.122 (9), p.1061-1066
• Main Authors: Huang, Mao, Liu, Xuan, DU, Qiang, Yao, Xin, Yin, Kai-sheng
• Format: Article
• Language: English
• Subjects: Angiogenesis Inhibitors - pharmacology; Animals; Asthma - chemically induced; Asthma - drug therapy; Asthma - immunology; Blotting, Western; Bronchial Hyperreactivity - chemically induced; Bronchial Hyperreactivity - immunology; Bronchoalveolar Lavage Fluid - chemistry; Female; Immunoglobulin E - blood; Immunohistochemistry; Immunoprecipitation; In Vitro Techniques; Indoles - pharmacology; Inflammation - chemically induced; Inflammation - immunology; Interleukin-13 - metabolism; Interleukin-4 - metabolism; Lung - drug effects; Lung - immunology; Lung - metabolism; Mice; Mice, Inbred BALB C; Ovalbumin - pharmacology; Proto-Oncogene Proteins c-kit - metabolism; Pyrroles - pharmacology; Th2细胞因子; 卵清蛋白; 受体酪氨酸激酶抑制剂; 哮喘小鼠; 实验性哮喘; 慢性哮喘; 抑制作用; 过敏性气道炎症
• ISSN: 0366-6999; 2542-5641
• DOI: 10.3760/cma.j.issn.0366-6999.2009.09.010

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.