| Lentiviral mediated IL-4 and IL-13 RNAi decrease airway inflammation and hyperresponsiveness. | |
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MedLine Citation:
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PMID: 21375458 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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Chen-Chen Lee; Hsin-Ying Huang; Bor-Luen Chiang |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-3-7 |
Journal Detail:
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Title: Human gene therapy Volume: - ISSN: 1557-7422 ISO Abbreviation: - Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-3-7 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9008950 Medline TA: Hum Gene Ther Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Taipei, Taiwan; leechenchen@mail.cmu.edu.tw. |
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