| Project/Area Number |
14570537
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | University of Tsukuba |
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Principal Investigator |
ISHII Yukio University of Tsukuba, Graduate School of Comprehensive Human Science, Assistant Professor, 大学院・人間総合科学研究科, 講師 (80272194)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2004: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | NKT cells / alpha-galactosylceramide / pulmonary fibrosis / bleomysin / interferon-gamma / Th1 / Th2 / Natural killer T細胞 / α-galactosylceramide / マウス / interferon-gamma |
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| Research Abstract |
Pulmonary fibrosis is an end-stage disorder for which efficacious therapeutic options are not readily available. Although its pathogenesis is poorly understood, pulmonary fibrosis occurs as a result of various inflammations. NKT cells modulate inflammation because of their ability to produce large amounts of cytokines by stimulation with their glycolipid ligand. In the present study, we investigated the effects of alpha-galactosylceramide (alpha-GalCer), a selective NKT cell ligand, on the development of bleomycin-induced pulmonary fibrosis. Treatment of mice with alpha-GalCer prolonged their survival under bleomycin administration by attenuating the development of pulmonary fibrosis. The protective effects of alpha-GalCer were associated with an increase in the pulmonary level of IFN-gamma and a decrease in the pulmonary level of fibrogenic cytokines such as TGF-beta and connective tissue growth factor. The initial pulmonary inflammation caused by bleomycin was also attenuated by alpha-GalCer with the reduction of the macrophage inflammatory protein-2 level. The protective effects of alpha-GalCer were markedly reduced in mice lacking NKT cells or as a result of treatment with anti-IFN-gamma antibody. These results suggest that alpha-GalCer suppresses bleomycin-induced acute pulmonary inflammation and thus attenuates the development of pulmonary fibrosis possibly by regulating several cytokine levels.
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