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Effects of antisense interleukin-5 gene transferred by recombinant adeno-associated virus to allergic rats.

Authors: Zeng, D  Cao, Y  Song, Q  Cao, C  Liu, X  Xu, Y  Xiong, W 
Citation: Zeng D, etal., Respirology. 2010 Jan;15(1):132-40. Epub 2009 Nov 30.
Pubmed: (View Article at PubMed) PMID:19947994
DOI: Full-text: DOI:10.1111/j.1440-1843.2009.01670.x

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.

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CRRD Object Information
CRRD ID: 4890938
Created: 2010-12-22
Species: All species
Last Modified: 2010-12-22
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.