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Adenovirus-mediated transfer of heme oxygenase-1 cDNA attenuates severe lung injury induced by the influenza virus in mice

Gene Therapy volume 8, pages 1499–1507 (2001)Cite this article

Abstract

Heme oxygenase-1 (HO-1) is an inducible heat shock protein that regulates heme metabolism to form bilirubin, ferritin and carbon monoxide. Based on recent evidence that HO-1 is involved in the resolution of inflammation by modulating apoptotic cell death or cytokine expression, the present study examined whether overexpression of exogenous HO-1 gene transfer provides a therapeutic effect on a murine model of acute lung injury caused by the type A influenza virus. We demonstrate herein that the transfer of HO-1 cDNA resulted in (1) suppression of both pathological changes and intrapulmonary hemorrhage; (2) enhanced survival of animals; and (3) a decrease of inflammatory cells in the lung. TUNEL analysis revealed that HO-1 gene transfer reduced the number of respiratory epithelial cells with DNA damage, and caspase assay suggested that HO-1 suppressed lung injury via a caspase-8-mediated pathway. These findings suggest the feasibility of HO-1 gene transfer to treat lung injury induced by a pathogen commonly seen in the clinical setting. Since oxidative stress and lung injury are involved in many lung disorders, such as pneumonia induced by a variety of microorganisms and pulmonary fibrosis, HO-1 may be useful for wider clinical applications in gene therapy targeting lung disorders including acute pneumonia and pulmonary fibrosis. Gene Therapy (2001) 8, 1499–1507.

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Authors and Affiliations

  1. First Department of Internal Medicine, Yokohama City University School of Medicine, Yokohama, Japan

    T Hashiba, M Suzuki, S Suzuki, S Inoue, T Tsuburai, T Matsuse & Y Ishigatubo

  2. Second Department of Pathology, Yokohama City University School of Medicine, Yokohama, Japan

    Y Nagashima

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  1. T Hashiba
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Hashiba, T., Suzuki, M., Nagashima, Y. et al. Adenovirus-mediated transfer of heme oxygenase-1 cDNA attenuates severe lung injury induced by the influenza virus in mice. Gene Ther 8, 1499–1507 (2001). https://doi.org/10.1038/sj.gt.3301540

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