TY - JOUR
T1 - H2-Ea deficiency is a risk factor for bleomycin-induced lung fibrosis in mice
AU - Du, Min
AU - Irani, Roxanna A.
AU - Stivers, David N.
AU - Lee, Sang Joon
AU - Travis, Elizabeth L.
PY - 2004/10/1
Y1 - 2004/10/1
N2 - 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 Ea (Hl-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 5.16% (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.
AB - 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 Ea (Hl-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 5.16% (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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U2 - 10.1158/0008-5472.CAN-04-1678
DO - 10.1158/0008-5472.CAN-04-1678
M3 - Article
C2 - 15466168
AN - SCOPUS:4944250274
SN - 0008-5472
VL - 64
SP - 6835
EP - 6839
JO - Cancer Research
JF - Cancer Research
IS - 19
ER -