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Lentiviral mediated IL-4 and IL-13 RNAi decrease airway inflammation and hyperresponsiveness.
MedLine Citation:
PMID:  21375458     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
IL-4 and IL-13 are two key cytokines released from activated T helper type 2 (Th2) cells and strongly associated with asthma and allergic disease. We applied silencing of the IL-4 and IL-13 gene expression by RNA interference (RNAi) delivered by a lentiviral vector to evaluate the therapeutic effect of IL-4 and IL13 short hairpin RNAs (shRNAs) in a murine model of asthma. Mice were sensitized with OVA and one treatment of IL-4 and IL-13 shRNAs lentiviral vector (Lenti-si-IL-4 and Lenti-si-IL-13) were instilled intratracheally 48h before challenge. After three challenges of OVA antigen, mice were assessed for airway inflammation and hyperresponsiveness. With infection of Lenti-si-IL-4 and Lenti-si-IL-13 in EL-4 cells, both RNA and protein expressions of IL-4 and IL-13 were obviously abrogated. Furthermore, intratracheal instillation of Lenti-si-IL-4 and Lenti-si-IL-13 in OVA-immunized mice resulted in a strong inhibition of local IL-4 and IL-13 cytokine releases. Treatment with Lenti-si-IL-4 and Lenti-si-IL-13 successfully alleviated OVA-induced airway eosinophilia and Th2 cells cytokines production. Finally, to determine airway hyperresponsiveness (AHR) by enhanced pause (Penh) and pulmonary resistance (RL) in non-invasive and invasive body plethysmography, we found that administration of Lenti-si-IL-4 and Lenti-si-IL-13 markedly decreased AHR in OVA-immunized mice. These results suggested that inhibition of IL-4 and IL-13 genes expression by shRNAs expression lentiviral vector markedly inhibited antigen-induced airway inflammation and hyperresponsiveness in mice.
Authors:
Chen-Chen Lee; Hsin-Ying Huang; Bor-Luen Chiang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-7
Journal Detail:
Title:  Human gene therapy     Volume:  -     ISSN:  1557-7422     ISO Abbreviation:  -     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-3-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9008950     Medline TA:  Hum Gene Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Taipei, Taiwan; leechenchen@mail.cmu.edu.tw.
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