title: Silencing of c-kit with small interference RNA attenuates inflammation             in a murine model of allergic asthma.
abstract: Asthma is a chronic respiratory disease characterized by the inﬂammation of the airways due to inﬁltration and activation of several inflammatory cells that produce cytokines. c-kit, a proto-oncogene that encodes a tyrosine kinase receptor, has been found to be associated with allergic inflammation. The aim of the present study was to assess whether silencing of c-kit with small interference RNA (siRNA) would attenuate inflammation in allergic asthma. A mouse model of ovalbumin (OVA)-induced allergic asthma was treated with systemic administration of anti-c-kit siRNA to inhibit the expression of the c-kit gene. siRNAs were injected through the vena caudalis. We measured inﬂammatory response in both anti-c-kit siRNA-treated and control mice. Systemic administration of siRNA could effectively inhibit the expression of the c-kit gene and reduce the infiltration of inflammatory cells (eosinophils and lymphocytes) into the lung tissue and bronchoalveolar lavage fluid. In addition, we found that c-kit siRNA can decrease the production of the T-helper type 2 (Th2) cytokines, interleukin 4 (IL-4) and IL-5, but has no influence on IFN-γ generation. These results show that inhibition of c-kit expression with siRNA can reduce the inflammatory response in allergic asthma.
authors.affiliation: Division of Pulmonary Diseases, State Key Laboratory of Biotherapy                     of China, and Department of Respiratory and Tuberculosis Medicine, West                     China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Jia-Jia
authors.initials: JJ
authors.lastname: Dong
authors.forename: Zeng-Lin
authors.initials: ZL
authors.lastname: Liao
authors.forename: Fu-Qiang
authors.initials: FQ
authors.lastname: Wen
mesh_terms: D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000628:therapy; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics* / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering
chemical_list: D015848:Interleukin-5; D034741:RNA, Small Interfering; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin; D019009:Proto-Oncogene Proteins c-kit