H2-Ea deficiency is a risk factor for bleomycin-induced lung fibrosis in mice.
Cancer Res
; 64(19): 6835-9, 2004 Oct 01.
Article
em En
| MEDLINE
| ID: mdl-15466168
ABSTRACT
Pulmonary fibrosis is a significant complication in cancer patients when treated by radiation, e.g., thoracic malignant diseases, or chemotherapeutic agents. Bleomycin is one of the primary drugs used to treat testicular cancer, but the incidence of significant pulmonary fibrosis limits the dose. It is known that susceptibility to bleomycin-induced pulmonary fibrosis is a heritable trait controlled by multiple genes, none of which, however, are yet known. In this study, we used expression profiling and genetic analysis in mouse models of bleomycin-induced pulmonary fibrosis and identified MHC class II antigen Ealpha (H2-Ea) as a risk factor for this disease. We found that a loss-of-function deletion in the H2-Ea gene was linked to susceptibility. A functional test of H2-Ea in transgenic mice showed 100% survival in the transgenic mice compared with 53% in C57BL/10J mice and significantly decreased pulmonary fibrosis from 16.42% (C57BL/10J) to 5.76% (transgenic; P = 1.20e(-8)). These results show that H2-Ea expression protects mice from bleomycin-induced pulmonary fibrosis, which implicates H2-Ea as a candidate susceptibility gene for pulmonary fibrosis.
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Base de dados:
MEDLINE
Assunto principal:
Fibrose Pulmonar
/
Bleomicina
/
Antígenos H-2
/
Genes MHC da Classe II
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Estados Unidos