Adenovirus-Mediated Transfer and Overexpression of Heme Oxygenase 1 cDNA in Lung Prevents Bleomycin-Induced Pulmonary Fibrosis via a Fas–Fas Ligand-Independent Pathway
2002; Mary Ann Liebert, Inc.; Volume: 13; Issue: 16 Linguagem: Inglês
10.1089/10430340260355356
ISSN1557-7422
AutoresTakahiro Tsuburai, Motoyoshi Suzuki, Yoji Nagashima, Shunsuke Suzuki, Satoshi Inoue, Tomonori Hashiba, Atsuhisa Ueda, Kunihiko Ikehara, Takeshi Matsuse, Yoshiaki Ishigatsubo,
Tópico(s)Restraint-Related Deaths
ResumoHeme oxygenase 1 (HO-1) is an inducible enzyme that catalyzes heme to generate bilirubin, ferritin, and carbon monoxide. Because enhanced expression of HO-1 confers protection against many types of cell and tissue damage by modulating apoptotic cell death or cytokine expression profiles, we hypothesized that adenovirus-mediated transfer of HO-1 cDNA and subsequent overexpression of the protein in lung would provide therapeutic benefit in a murine model of bleomycin-induced pulmonary fibrosis. In C57BL/6 mice, HO-1 overexpression clearly suppressed the development of fibrotic changes and was associated with enhanced interferon gamma production in lung and reduced numbers of respiratory epithelial cells with damaged DNA. However, HO-1 overexpression did not prevent pulmonary fibrosis induced by agonistic anti-Fas antibody inhalation in C57BL/6 or ICR mice, a strain known to develop pulmonary fibrosis via the Fas-Fas ligand (FasL) pathway. Consistent with the concept that HO-1 overexpression prevents fibrosis via a pathway independent of Fas-FasL interaction, Ad.HO-1 administration prevented bleomycin-induced pulmonary fibrosis in gld/gld mice, which express nonfunctional FasL. These observations suggest that using HO-1 overexpression strategies to treat idiopathic pulmonary fibrosis, or fibrotic disorders of other target organs, by attenuating apoptotic cell death likely would be effective in clinical situations.
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