title: Intranasal sirna targeting c-kit reduces airway inflammation in experimental allergic asthma.
abstract: Allergic asthma is characterized by airway inflammation caused by infiltration and activation of inflammatory cells that produce cytokines. Many studies have revealed that c-kit, a proto-oncogene, and its ligand, stem cell factor (SCF), play an important role in the development of asthmatic inflammation. Intranasal small interference RNA (siRNA) nanoparticles targeting specific viral gene could inhibit airway inflammation. In this study, we assessed whether silencing of c-kit with intranasal small interference RNA could reduce inflammation in allergic asthma. A mouse model of experimental asthma was treated with intranasal administration of anti-c-kit siRNA to inhibit the expression of the c-kit gene. We assessed the inflammatory response in both anti-c-kit siRNA-treated and control mice. Local administration of siRNA effectively inhibited the expression of the c-kit gene and reduced airway mucus secretion and the infiltration of eosinophils in bronchoalveolar lavage fluid. Moreover, c-kit siRNA reduced the production of SCF, interleukin-4 (IL-4), and IL-5, but had no effect on interferon-γ (IFN-γ) generation. These results show that intranasal siRNA nanoparticles targeting c-kit can decrease the inflammatory response in experimental allergic asthma.
authors.affiliation: Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Xi'an Medical University Xi'an, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Xi'an Medical University Xi'an, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Xi'an Medical University Xi'an, China.
authors.forename: Ya-Ming
authors.initials: YM
authors.lastname: Li
authors.affiliation: Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Xi'an Medical University Xi'an, China.
authors.forename: Sheng-Yu
authors.initials: SY
authors.lastname: Wang
authors.affiliation: Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Xi'an Medical University Xi'an, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Diao
authors.affiliation: Department of Laboratory Medicine, The Affiliated Hospital of Xi'an Medical University Xi'an, China.
authors.forename: Kai-Ge
authors.initials: KG
authors.lastname: Liu
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004195:Disease Models, Animal; D015536:Down-Regulation; D015316:Genetic Therapy / Q000379:methods*; D018836:Inflammation Mediators / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D053758:Nanoparticles; D010047:Ovalbumin; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage*
chemical_list: D018836:Inflammation Mediators; D015848:Interleukin-5; D034741:RNA, Small Interfering; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin; D019009:Proto-Oncogene Proteins c-kit
keywords: asthma; c-kit; gene silencing; inflammation; small interference RNA