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

Citation
T. Hashiba et al., Adenovirus-mediated transfer of heme oxygenase-1 cDNA attenuates severe lung injury induced by the influenza virus in mice, GENE THER, 8(19), 2001, pp. 1499-1507
Citations number
63
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
GENE THERAPY
ISSN journal
0969-7128 → ACNP
Volume
8
Issue
19
Year of publication
2001
Pages
1499 - 1507
Database
ISI
SICI code
0969-7128(200110)8:19<1499:ATOHOC>2.0.ZU;2-5
Abstract
Heme oxygenase-1 (HO-1) is an inducible heat shock protein that regulates h eme metabolism to form bilirubin, ferritin and carbon monoxide. Based on re cent evidence that HO-1 is involved in the resolution of inflammation by mo dulating apoptotic cell death or cytokine expression, the present study exa mined whether overexpression of exogenous HO-1 gene transfer provides a the rapeutic 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 resu lted in (1) suppression of both pathological changes and intrapulmonary hem orrhage; (2) enhanced survival of animals; and (3) a decrease of inflammato ry cells in the lung. TUNEL analysis revealed that HO-1 gene transfer reduc ed the number of respiratory epithelial cells with DNA damage, and caspase assay suggested that HO-1 suppressed lung injury via a caspase-8-mediated p athway. These findings suggest the feasibility of HO-1 gene transfer to tre at 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 fi brosis, HO-1 may be useful for wider clinical applications in gone therapy targeting lung disorders including acute pneumonia and pulmonary fibrosis.