Recombinant adeno-associated virus vector-mediated delivery of antisense interleukin-5 gene attenuates airway remodeling in allergic rats.
BACKGROUND
Increasing evidence indicates that eosinophils contribute greatly to airway remodeling in asthma. Since interleukin-5 (IL-5) plays a critical role in the regulation of eosinophils in asthma, anti-IL-5 therapy may be a novel approach to inhibit airway remodeling in asthma.


OBJECTIVE
In this study, we applied a recombinant adeno-associated virus vector-mediated antisense IL-5 gene delivery (rAAV-ASIL-5) system to investigate its effect on airway remodeling in ovalbumin (OVA)-sensitized and -challenged rats.


METHODS
rAAV-ASIL-5 was used to infect OVA-sensitized and -challenged rats. IL-5 protein in bronchoalveolar lavage fluid (BALF) was detected by ELISA. The eosinophils in BALF were counted. Transforming growth factor (TGF)-β1- and TGF-β2-positive cells in the peribronchial space were detected by immunohistochemical staining. Lung tissue was collected for Sirius red staining and histological analysis.


RESULTS
rAAV-ASIL-5 significantly decreased the level of IL-5 protein, the number of eosinophils in BALF and the numbers of TGF-β1- and TGF-β2-positive cells in the peribronchial space. The area of Sirius red staining in airways was also decreased. Moreover, the rAAV-ASIL-5 treatment inhibited the increase in total bronchial wall area and airway smooth muscle area.


CONCLUSIONS
These results suggest that rAAV-ASIL-5-based gene therapy could be used to inhibit airway remodeling in allergic rats.
Zeng
Daxiong
D
Department of Respiratory Medicine, Tongji Hospital, Key Laboratory of Pulmonary Diseases of the Ministry of Health of China, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
Cao
Yong
Y
Song
Qingfeng
Q
Cao
Chao
C
Xie
Min
M
Liu
Xiansheng
X
Xiong
Shengdao
S
Xu
Yongjian
Y
Xiong
Weining
W
D056151:Airway Remodeling / Q000187:drug effects*; D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016373:DNA, Antisense / Q000235:genetics*; D000229:Dependovirus / Q000235:genetics*; D004804:Eosinophils / Q000276:immunology; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D015848:Interleukin-5 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D010047:Ovalbumin / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011995:Recombination, Genetic; D016896:Treatment Outcome
D016373:DNA, Antisense; D015848:Interleukin-5; D010047:Ovalbumin