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. Objectives: 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. Conclusion: These results suggest that rAAV-ASIL-5-based gene therapy could be used to inhibit airway remodeling in allergic rats.