| Project/Area Number |
17591000
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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 | Yamaguchi University |
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Principal Investigator |
KAWANO Michio (2006) Yamaguchi University, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (40161343)
津山 尚宏 (2005) 山口大学, 大学院・医学系研究科, 助手 (10335747)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIKAWA Hideaki Yamaguchi University, Graduate School of Medicine, Associate Professor, 大学院医学系研究科, 助教授 (40294623)
OBATA Masanori Yamaguchi University, Graduate School of Medicine, Assistant Professor, 大学院医学系研究科, 講師 (80158831)
河野 道生 山口大学, 大学院・医学系研究科, 教授 (40161343)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2005: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | myeloma cells / CD45 / CD45R0 / CD45RA / lipid rafts / signal transduction / Galectin-1 / IL-6 / 骨髄腫 / CD-45 |
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| Research Abstract |
Human myeloma cells show the different surface antigen expressions from those in norma bone marrow plasma cells; especially, all normal plasma cells express CD45, CD45RA, but most myeloma cells do not express CD45 and a small subpopulation of myeloma cells express CD45, CD45R0 but not CD45RA. Myeloma cells respond to interleukin 6(IL-6) to proliferate, and this IL-6-induced proliferation of myeloma cells requires CD45, CD45R0 on their surface. In order to clarify the role of CD45 (CD45R0) on the IL-6-induced proliferation, we investigated how CD45R0 or CD45RA translocated to lipid rafts after IL-6 stimulation in human myeloma cell lines. CD45R0 rapidly translocated to lipid rafts after IL-6 stimulation, while CD45RA remained outside of lipd rafts. The presence of CD45RA induced the suppression of intracellular signaling induced by IL-6, especially the downregulation of phosphorylation of ERK. Also, we investigated what molecules could bind to CD45RA but not CD45R0 extracellularly ; Galectin-1 could bind to CD45RA but not CD45RO, and induced the suppression of IL-6-induced proliferation. Therefore, these results suggest that IL-6-induced proliferation of myeloma cells is regulated by CD45RO, and CD45RA has the inhibitory effect on IL-6-induced proliferation and the mechanism of the inhibitory effect of CD45RA may be due to the blockade of translocation to lipid rafts and the extracellualr binding of Galectin-1.
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