2004 Fiscal Year Final Research Report Summary
Anti-IL-6 activity of Notch signal : development of new therapeutic approaches for multiple myeloma
| Project/Area Number |
15591001
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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 |
Hematology
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| Research Institution | Mie University |
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Principal Investigator |
KATAYAMA Naoyuki Mie University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (20185812)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Langerhans cells / Notch signal / Monocytes / Human / GM-CSF / TGF-β |
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| Research Abstract |
IL-6 is widely recognized as a major cytokine that stimulates the proliferation of myeloma cells through paracrine and autocrine mechanisms. We previously reported that IL-6 inhibits the differentiation of human blood monocytes into dermal dendritic cells. It is possible that IL-6 produced by myeloma cells is at least in part involved in the immune deficiency in patients with multiple myeloma. Our objective when we began this study was to restore the immune deficiency associated with multiple myeloma through anti-IL-6 signals. During the study, we incidentally found that the immobilized Notch ligand Delta-1 plays a crucial role in the differentiation of human blood monocytes into Langerhans cells. Recently, it was reported that Notch ligand Delta-1 is expressed in a proportion of the skin. GM-CSF and TGF-β1 are also secreted in the skin. We report here that Notch ligand Delta-1, in concert with GM-CSF and TGF-β1, induces the differentiation of human CD14^+ blood monocytes into cells th
… More
at express Langerhans cell markers : CD1a, Langerin, cutaneous lymphocyte-associated antigen, CC chemokine receptor 6, and E-cadherin. By transmission electron microscopy, the cells exhibited long prominent dendrites homogenously distributed on the cell surface and contained multiple organelles. Rod-or racket-shaped Birbeck granules with central lamella were encountered at a high frequency in the cell profiles. The cells display the phagocytic activity. In response to CD40 ligand and TNF-α, the cells acquire a mature phenotype of dendritic cells that is characterized by upregulation of HLA-ABC,HLA-DR,CD80,CD86,CD40,and CD54, and appearance of CD83. These cells elicit activation of CD8^+ T cells and Th1 polarization of CD4^+ T cells. Thus, human blood monocytes can be instructed to differentiate into Langerhans cells upon exposure to Notch ligand Delta-1,GM-CSF,and TGF-β1,which may be in part relevant to the development of human epidermal Langerhans cells. Our results not only extend the functional scope of Notch ligand Delta-1 in human hematopoiesis but also provide with the possibility to apply Langerhans cells to cellular immunotherapy for hematological malignancies such as multiple myeloma. Less
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Research Products
(16 results)
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[Journal Article] IL-4 and IL-10 synergistically inhibit survival of human blood monocytes supported by GM-CSF.2005
Author(s)
Miyashita H, Katayama N, Fujieda A, Shibasaki T, Yamamura K, Sugimoto Y, Miyata E, Ohishi K, Nishii K, Masuya M, Shiku H
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Journal Title
IntJ Oncol 26・3
Pages: 731-735
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Acute myeloid leukemia with t(8;21)(q22;q22) manifesting as granulocytic sarcoma in the rhinopharynx and external acoustic meatus at relapse after high-dose cytarabine : case report and review of the literature.2004
Author(s)
Sugimoto Y, Nishii K, Sakakura M, Araki H, Usui E, Lorenzo FV, Hoshino N, Miyashita H, Ohishi K, Katayama N, Shiku H
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Journal Title
Hematol J 5・1
Pages: 84-89
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Reprogramming of human postmitotic neutrophils into macrophages by growth factors.2004
Author(s)
Araki H, Katayama N, Yamashita Y, Mano H, Fujieda A, Usui E, Mitani H, Ohishi K, Nishii K, Masuya M, Minami N, Nobori T, Shiku H
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Journal Title
Blood 103・8
Pages: 2973-2980
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Activities of granulocyte-macrophage colony-stimulating factor and interleukin-3 on monocytes.2004
Author(s)
Suzuki H, Katayama N, Ikuta Y, Mukai K, Fujieda A, Mitani H, Araki H, Miyashita H, Hoshino N, Nishikawa H, Nishii K, Minami N, Shiku H
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Journal Title
Am J Hematol 75・4
Pages: 179-189
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Fluorescent in situ hybridization analysis of Philadelphia chromosome-negative chronic myeloid leukemia with the bcr/abl fusion gene.2004
Author(s)
Monma F, Nishii K, Yamamori S, Hosokai N, Nakazaki T, Lorenzo FV, Usui E, Sakakura M, Miyashita H, Fujieda A, Ohishi K, Katayama N, Shiku H
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Journal Title
Int J Hematol 80・2
Pages: 155-158
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Characteristics of t(8;21) acute myeloid leukemia(AML) with additional chromosomal abnormality : concomitant trisomy 4 may constitute a distinctive subtype of t(8;21) AML.2003
Author(s)
Nishii K, Usui E, Katayama N, Lorenzo FV, Nakase K, Kobayashi T, Miwa H, Mizutani M, Tanaka I, Nasu K, Dohy H, Kyo T, Taniwaki M, Ueda T, Kita K, Shiku H
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Journal Title
Leukemia 17・4
Pages: 731-737
Description
「研究成果報告書概要(欧文)」より
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[Book] 血液病学2005
Author(s)
片山直之, 珠玖 洋
Publisher
文光堂(印刷中)
Description
「研究成果報告書概要(和文)」より
