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Lentiviral mediated IL-4 and IL-13 RNAi decrease airway inflammation and hyperresponsiveness.

Authors: Lee, CC  Huang, HY  Chiang, BL 
Citation: Lee CC, etal., Hum Gene Ther. 2011 Mar 7.
Pubmed: (View Article at PubMed) PMID:21375458
DOI: Full-text: DOI:10.1089/hum.2009.105

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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CRRD Object Information
CRRD ID: 5128557
Created: 2011-03-08
Species: All species
Last Modified: 2011-03-08
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.