| Project/Area Number |
20590081
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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 |
Biological pharmacy
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| Research Institution | National Institute of Infectious Diseases |
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Principal Investigator |
MASUMI Atsuko National Institute of Infectious Diseases, 血液・安全性研究部, 主任研究官 (70165728)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | インターフェロン制御転写因子 / 造血幹細胞 / 血液細胞分化 / インターフェロン制御因子 / IFN / インターフェロン / IRF-2 / 転写因子 / 骨髄細胞 |
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| Research Abstract |
Megakaryopoiesis is associated with inflammation, and certain inflammatory cytokines stimulate hematopoietic progenitors to differentiate into megakaryocytes. Interferon-γ (IFN-γ) is an inflammatory cytokine that stimulates megakaryocyte development, and interferon regulatory factors (IRFs), IRF-1 and IRF-2 are typical transcription factors that are involved in IFN-γ response. We investigate the role of IRFs in megakaryopoiesis. To investigate the role of IRFs in megakaryopoiesis, mouse bone marrow hematopoietic stem cells (HSCs) were prepared and stimulated with IFN-γ. IFN-γ treatment induced IRF-2 expression as well as CD41 although their induction levels were much lower than that of IRF-1. When IRF expression levels were studied in mouse bone marrow cell fractions, IRF-2 expression was relatively high in HSCs. An in vitro clonogenic assay showed that IRF-2 overexpressed cells increased the number of megakaryocytic colonies, but not IRF-1 overexpressed cells, suggesting that IRF-2 is involved in megakaryopoiesis. Mechanistic analysis showed that IRF-2 transfection up-regulated CD41 promoter activity in hematopoietic cell lines through its binding to an ISRE-like site in the CD41 promoter. These findings suggest that IRF-2 plays an important role in megakaryocytic cell commitment or differentiation from hematopoietic stem cells by regulating CD41 expression in an inflammation state.
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