| Project/Area Number |
21590965
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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 | Kobe University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
KOTANI Yoshikazu 神戸大学, 大学院・医学研究科, 講師 (90403287)
FUNADA Yasuhiro 神戸大学, 医学部附属病院, 助教 (60437465)
KOBAYASHI Kazuyuki 神戸大学, 大学院・医学研究科, 特命講師 (50403275)
OKADA Taro 神戸大学, 大学院・医学研究科, 准教授 (80304088)
NISHIUMA Teruaki 神戸大学, 大学院・医学研究科, 研究員 (10379414)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2009: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | スフィンゴシン / 気管支喘息 / 粘液産生 / Sphingosine kinase / SlP受容体 / Shingosine kinase / S1P受容体 / mucin / ERK / IL-13 / goblet cells |
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| Research Abstract |
We cultured normal human bronchial epithelial cells in an air-liquid interface and treated with IL-13 to induce their differentiation into goblet cells. Sphingosinekinase1(SphK1) and MUC5AC expression was increased by IL-13 treatment at both protein and mRNA levels. N, N-dimethylsphingosine(DMS), a potent SphK inhibitor, decreased MUC5AC expression up-regulated by IL-13 treatment. DMS inhibited IL-13-induced ERK1/2 phosphorylation. These results suggest that SphK1 is involved in MUC5AC production induced by IL-13 upstream of ERK1/2 phosphorylation, and independent of STAT6 phosphorylation.
Next we utilized the mouse asthmatic model and found that both SphK and MUC5AC expression were increased and co-localized in airway epithelium. The number of eosinophil and eosinophil peroxidase activity, levels of cytokine were improved by administration of DMS, SphK inhibitor, and FTY-720, sphingosine 1-phosphate agonist, without worsening pulmonary vascular permeability.
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