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Adenovirus expressing Fas ligand gene decreases airway hyper-responsiveness and eosinophilia in a murine model of asthma

Gene Therapy volume 11, pages 1497–1505 (2004)Cite this article

Abstract

Allergic asthma is characterized by airway hyper-responsiveness (AHR) and cellular infiltration of the airway with predominantly eosinophils and Th2 cells. The normal resolution of inflammation in the lung occurs through the regulated removal of unneeded cells by Fas–Fas ligand-mediated apoptosis. Fas ligand (FasL) is a member of the tumor necrosis factor family, and when bound to Fas, it induces apoptosis of the cells. To examine the effect of the FasL gene on airway inflammation and immune effector cells in allergic asthma, recombinant adenovirus expressing murine FasL (Ad-FasL) was delivered intratracheally into ovalbumin (OVA)-immunized mice. We found that a single administration of Ad-FasL in OVA-immunized mice significantly alleviated AHR and eosinophilia by inducing the apoptosis of eosinophils and/or reducing eosinophil attractant factors, such as IL-5 and eotaxin levels. The number of infiltrated lymphocytes and Th2 cytokines, including IL-5 and IL-13, decreased in OVA-immunized mice by administration of Ad-FasL. KC and TNF-α production also decreased in Ad-FasL-treated OVA-immunized mice. These findings indicated that the administration of Ad-FasL to OVA-sensitized mice significantly suppressed pulmonary allergic responses. Although more studies are needed, these results suggested that Ad-FasL might be applied as an alternative therapy for allergic asthma.

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Acknowledgements

This work was supported by a grant from the National Science Council of the Republic of China.

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Authors and Affiliations

  1. Graduate Institute of Immunology, Taipei, Taiwan, Republic of China

    Y-H Chuang, C-L Fu & B-L Chiang

  2. Department of Pediatrics, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China

    Y-C Lo & B-L Chiang

  3. Department of Pediatrics, Chung-Hsin Municipal Hospital, Taipei, Taiwan, Republic of China

    Y-C Lo

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Chuang, YH., Fu, CL., Lo, YC. et al. Adenovirus expressing Fas ligand gene decreases airway hyper-responsiveness and eosinophilia in a murine model of asthma. Gene Ther 11, 1497–1505 (2004). https://doi.org/10.1038/sj.gt.3302325

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