title: Recombinant adeno-associated virus vector-mediated delivery of antisense interleukin-5 gene attenuates airway remodeling in allergic rats.
abstract: 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.
authors.affiliation: 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.
authors.forename: Daxiong
authors.initials: D
authors.lastname: Zeng
authors.forename: Yong
authors.initials: Y
authors.lastname: Cao
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Song
authors.forename: Chao
authors.initials: C
authors.lastname: Cao
authors.forename: Min
authors.initials: M
authors.lastname: Xie
authors.forename: Xiansheng
authors.initials: X
authors.lastname: Liu
authors.forename: Shengdao
authors.initials: S
authors.lastname: Xiong
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Xu
authors.forename: Weining
authors.initials: W
authors.lastname: Xiong
mesh_terms: 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
chemical_list: D016373:DNA, Antisense; D015848:Interleukin-5; D010047:Ovalbumin