Attenuation of bleomycin-induced pneumopathy in mice by a caspase inhibitor.
Am J Physiol Lung Cell Mol Physiol
; 280(2): L316-25, 2001 Feb.
Article
in En
| MEDLINE
| ID: mdl-11159011
ABSTRACT
Caspases have been implicated in the effector process of apoptosis in several systems including the Fas-Fas ligand pathway. We previously demonstrated that excessive apoptosis of lung epithelial cells and the Fas-Fas ligand pathway were essential in the pathogenesis of bleomycin-induced pneumopathy in mice. Therefore, the purpose of this study was to investigate whether a caspase inhibitor could prevent the development of this model. The expression of caspase-1 and caspase-3 was upregulated on lung epithelial cells, alveolar macrophages, and infiltrating inflammatory cells in this model. We demonstrated that a broad-spectrum caspase inhibitor, N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone, decreased the caspase-1- and caspase-3-like activity, the number of apoptotic cells, the pathological grade of lung inflammation and fibrosis, and the hydroxyproline content in lung tissues in this model. We conclude that caspase inhibitors could be a new therapeutic approach against lung injury and pulmonary fibrosis.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pulmonary Fibrosis
/
Bleomycin
/
Caspase Inhibitors
/
Amino Acid Chloromethyl Ketones
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Am J Physiol Lung Cell Mol Physiol
Journal subject:
BIOLOGIA MOLECULAR
/
FISIOLOGIA
Year:
2001
Document type:
Article
Affiliation country:
Japan