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Adenovirus-mediated interferon gamma gene therapy for allergic asthma: involvement of interleukin 12 and STAT4 signaling.

Authors: Behera, AK  Kumar, M  Lockey, RF  Mohapatra, SS 
Citation: Behera AK, etal., Hum Gene Ther. 2002 Sep 20;13(14):1697-709.
Pubmed: (View Article at PubMed) PMID:12396623
DOI: Full-text: DOI:10.1089/104303402760293547

Allergic asthma is associated with airway inflammation and hyperresponsiveness caused by the dysregulated production of cytokines secreted by allergen-specific helper T type 2 (Th2) cells. Allergic subjects produce relatively low amounts of interferon gamma (IFN-gamma), a pleiotropic Th1 cytokine that downregulates Th2-associated responses. In this study, we examined the possibility of modulating ovalbumin (OVA)-induced inflammation and airway hyperreactivity (AHR) by recombinant adenovirus-mediated IFN-gamma (Ad-IFN-gamma) gene transfer. OVA-sensitized mice treated with Ad-IFN-gamma exhibit significantly lower levels of Th2 cytokines interleukin 4 (IL-4) and IL-5, OVA-specific serum IgE, lung eosinophilia, and AHR in response to methacholine challenge compared with control mice. The lung sections of the treated mice show less epithelial damage, mucous plugging, and eosinophil infiltration than controls. In contrast, Ad-IFN-gamma-treated mice express significantly higher levels of IFN-gamma and IL-12 when compared with controls. Moreover, administration of Ad-IFN-gamma to mice with established AHR significantly reduced AHR, Th2 cytokines, and lung inflammation. The IFN-gamma effects were dependent on IL-12 and STAT4 (signal transducer and activator of transcription 4), as mice treated with antibodies to IL-12 and STAT4 deficient mice show attenuated Ad-IFN-gamma responses. Thus, these results demonstrate that mucosal Ad-IFN-gamma gene transfer can effectively attenuate established allergen-induced airway inflammation and AHR, predominantly through an IL-12- and STAT4-dependent mechanism.

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CRRD Object Information
CRRD ID: 10755706
Created: 2016-02-03
Species: All species
Last Modified: 2016-02-03
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.