Huang Mao, Liu Xuan, DU Qiang, Yao Xin, Yin Kai-sheng
Department of Respiratory Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
Chin Med J (Engl). 2009 May 5;122(9):1061-6.
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.
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.
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.
Sunitinib may inhibit the development of airway inflammation, AHR and airway remodeling. It is potentially beneficial to the prevention or treatment of asthma.
酪氨酸激酶信号级联在过敏性气道炎症的发病机制中起关键作用。据报道，多靶点受体酪氨酸激酶抑制剂舒尼替尼具有强大的免疫调节、抗炎和抗纤维化作用。我们研究了舒尼替尼是否能抑制慢性哮喘小鼠模型中气道炎症、气道高反应性（AHR）和气道重塑的进展。
用卵清蛋白（OVA）致敏小鼠，并用雾化OVA进行8周的慢性激发。在OVA激发期间，一些小鼠每天经胃给予舒尼替尼（40mg/kg）。在最后一次OVA激发后12小时，评估小鼠气道炎症、AHR和气道重塑的发展情况。通过酶联免疫吸附测定（ELISA）测量支气管肺泡灌洗液（BALF）中总血清免疫球蛋白E（IgE）和Th2细胞因子（白细胞介素（IL）-4和IL-13）的水平。通过免疫沉淀/蛋白质印迹（IP/WB）分析检测肺中磷酸化c-kit蛋白的表达。
舒尼替尼显著抑制慢性实验性哮喘中的嗜酸性气道炎症、持续性AHR和气道重塑。它降低了总血清IgE水平和BALF中Th2细胞因子水平，还降低了重塑气道中磷酸化c-kit蛋白的表达。
舒尼替尼可能抑制气道炎症、AHR和气道重塑的发展。它对哮喘的预防或治疗可能有益。
