Wu Wei, Chen Hui, Li Ya-Ming, Wang Sheng-Yu, Diao Xin, Liu Kai-Ge
Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Xi'an Medical University Xi'an, China.
Department of Laboratory Medicine, The Affiliated Hospital of Xi'an Medical University Xi'an, China.
Int J Clin Exp Pathol. 2014 Aug 15;7(9):5505-14. eCollection 2014.
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.
过敏性哮喘的特征是由产生细胞因子的炎症细胞浸润和激活所引起的气道炎症。许多研究表明，原癌基因c-kit及其配体干细胞因子（SCF）在哮喘炎症的发展中起重要作用。靶向特定病毒基因的鼻内小干扰RNA（siRNA）纳米颗粒可抑制气道炎症。在本研究中，我们评估了鼻内小干扰RNA沉默c-kit是否能减轻过敏性哮喘的炎症。用鼻内给予抗c-kit siRNA治疗实验性哮喘小鼠模型，以抑制c-kit基因的表达。我们评估了抗c-kit siRNA治疗小鼠和对照小鼠的炎症反应。局部给予siRNA有效抑制了c-kit基因的表达，并减少了气道黏液分泌以及支气管肺泡灌洗液中嗜酸性粒细胞的浸润。此外，c-kit siRNA减少了SCF、白细胞介素-4（IL-4）和IL-5的产生，但对干扰素-γ（IFN-γ）的产生没有影响。这些结果表明，靶向c-kit的鼻内siRNA纳米颗粒可减轻实验性过敏性哮喘的炎症反应。
