These authors contributed equally to this study.
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Effects of antisense interleukin-5 gene transferred by recombinant adeno-associated virus to allergic rats
Article first published online: 30 NOV 2009
DOI: 10.1111/j.1440-1843.2009.01670.x
© 2009 The Authors. Journal compilation © 2009 Asian Pacific Society of Respirology
Additional Information
How to Cite
ZENG, D., CAO, Y., SONG, Q., CAO, C., LIU, X., XU, Y. and XIONG, W. (2010), Effects of antisense interleukin-5 gene transferred by recombinant adeno-associated virus to allergic rats. Respirology, 15: 132–140. doi: 10.1111/j.1440-1843.2009.01670.x
Publication History
- Issue published online: 27 DEC 2009
- Article first published online: 30 NOV 2009
- Received 9 January 2009; invited to revise 8 February 2009, 26 May 2009, 24 July 2009; revised 7 May 2009, 4 July 2009, 27 July 2009; accepted 31 July 2009 (Associate Editor: Takahide Nagase).
- Abstract
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Keywords:
- adeno-associated virus;
- airway inflammation;
- asthma;
- eosinophils;
- gene therapy;
- interleukin-5
An antisense IL-5 gene transferred by recombinant adeno-associated virus (rAAV-ASIL-5) was transfected into allergic rats. rAAV-ASIL-5 reduced the expression of IL-5, suppressed the recruitment and activation of eosinophils, decreased the levels of ECP, eotaxin and IgE and inhibited airway inflammation. rAAV-ASIL-5-based gene therapy may be useful in the treatment of allergic asthma.
ABSTRACT
Background and objective: The accumulation of eosinophils in airways is an important characteristic of asthma. The process is primarily mediated by interleukin-5 (IL-5) secreted by Th2 lymphocytes. This study explored a new approach to asthma therapy in which allergic rats were transfected with the IL-5 antisense gene delivered by the recombinant adeno-associated virus (rAAV-ASIL-5).
Methods: The viral vector rAAV-ASIL-5 was constructed and the IL-5 antisense gene transfected into allergic rats. The levels of IL-5, IgE, eotaxin and eosinophilic cationic protein (ECP) in sera and bronchoalveolar lavage fluid (BALF) were measured by ELISA. The inflammatory responses in lung tissues were evaluated by histological study.
Results: The levels of IL-5 protein in serum and BALF were significantly decreased in the allergic rats treated with rAAV-ASIL-5 (P < 0.05). Serum ovalbumin-specific IgE was reduced in treated rats compared with untreated rats (P < 0.05). rAAV-ASIL-5 treatment also reduced eosinophils in the peripheral blood and BALF, as well as the ECP and eotaxin levels in serum and BALF (P < 0.05). There was significantly less inflammation in the lungs of rAAV-ASIL-5-treated rats than in those of untreated rats. No obvious pathological damage to the kidneys and livers of the rats treated with rAAV was observed.
Conclusions: Treatment with rAAV-ASIL-5 inhibited the accumulation of eosinophils and airway inflammation in the rat model of allergic asthma by suppressing IL-5 production. These results suggest that rAAV-ASIL-5-based gene therapy may be used for the treatment of allergic asthma.