Inhibitory effects of sunitinib on ovalbumin-induced chronic experimental asthma in mice / 中华医学杂志(英文版)
Mao HUANG; Xuan LIU; Qiang DU; Xin YAO; Kai-sheng YIN.
Chinese Medical Journal
; (24): 1061-1066, 2009.
Artículo
en Inglés
| WPRIM | ID: wpr-279783
<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>Sunitinib may inhibit the development of airway inflammation, AHR and airway remodeling. It is potentially beneficial to the prevention or treatment of asthma.</p>
Asunto(s)
Animales Femenino Ratones Inhibidores de la Angiogénesis Farmacología Asma Quimioterapia Alergia e Inmunología Western Blotting Hiperreactividad Bronquial Alergia e Inmunología Líquido del Lavado Bronquioalveolar Química Inmunoglobulina E Sangre Inmunohistoquímica Inmunoprecipitación Técnicas In Vitro Indoles Farmacología Inflamación Alergia e Inmunología Interleucina-13 Metabolismo Interleucina-4 Metabolismo Pulmón Alergia e Inmunología Metabolismo Ratones Endogámicos BALB C Ovalbúmina Farmacología Proteínas Proto-Oncogénicas c-kit Metabolismo Pirroles Farmacología
Biblioteca responsable:
WPRO
powered by iAHx-2.18-89
Biblioteca Virtual en Salud