小发夹RNA
卵清蛋白
嗜酸性粒细胞趋化因子
免疫学
RNA干扰
基因沉默
嗜酸性粒细胞
发病机制
医学
支气管肺泡灌洗
哮喘
生物
核糖核酸
免疫系统
肺
内科学
基因
生物化学
作者
Ching-Jen Yang,Yu-Kuo Liu,Chao-Lin Liu,Chia–Ning Shen,Ming‐Ling Kuo,Chi-Wen Su,Ching Ping Tseng,Tzu‐Chen Yen,Chia–Rui Shen
出处
期刊:Human Gene Therapy
[Mary Ann Liebert]
日期:2009-12-01
卷期号:20 (12): 1597-1606
被引量:51
摘要
Asthma, a chronic helper T cell type 2-mediated inflammatory disease, is characterized by airway hyperresponsiveness and inflammation. Growing evidence suggests that increased expression of acidic mammalian chitinase (AMCase) may play a role in the pathogenesis of asthma. In the present study, we sought to develop an RNA interference approach to suppress allergic asthma in mice through silencing of AMCase expression. Mice sensitized with ovalbumin (OVA) were intratracheally administered a recombinant adeno-associated virus expressing short hairpin RNA (rAAV-shRNA) against AMCase. In OVA-sensitized mice, the development of allergic symptoms was significantly associated with elevated AMCase expression. After administration of rAAV-shRNA, there was a significant reduction of AMCase expression in the lung and in bronchoalveolar lavage fluid (BALF) cells of sensitized mice. Sensitized mice receiving rAAV-shRNA showed a significant improvement in allergic symptoms, including airway hyperresponsiveness (AHR), eosinophil infiltration, eotaxin, interleukin-13 secretion in BALF, and serum OVA-specific IgE level. Our data suggest the hyperexpression of AMCase in asthma can be suppressed by rAAV-mediated shRNA. Silencing AMCase expression by shRNA may be a promising therapeutic strategy in asthma.
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