Inhibition of acidic mammalian chitinase by RNA interference suppresses ovalbumin-sensitized allergic asthma.
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.
Yang
Ching-Jen
CJ
Department of Chemical and Materials Engineering, Chang Gung University, Taoyuan 333, Taiwan.
Liu
Yu-Kuo
YK
Liu
Chao-Lin
CL
Shen
Chia-Ning
CN
Kuo
Ming-Ling
ML
Su
Chien-Chang
CC
Tseng
Ching-Ping
CP
Yen
Tzu-Chen
TC
Shen
Chia-Rui
CR
D016475:3T3 Cells; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D002688:Chitinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D034622:RNA Interference
D010047:Ovalbumin; C499255:AMCase, mouse; D002688:Chitinases