| Project/Area Number |
11470171
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Yamaguchi University |
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Principal Investigator |
FURUKAWA Susumu Yamaguchi University, School of Medicine, Professor, 医学部, 教授 (30095830)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIWARA Motoki Yamaguchi University, Hospital, Assistant Professor, 医学部・附属病院, 講師 (90284257)
ICHIYAMA Takashi Yamaguchi University, Hospital, Assistant Professor, 医学部・附属病院, 講師 (20263767)
MATSUBARA Tomoyo Yamaguchi University, School of Medicine, Associate Professor, 医学部, 助教授 (10245722)
KOGA Mayumi Yamaguchi University, Hospital, Assistant Professor, 医学部・附属病院, 講師 (40263785)
INOUE Tamotsu Yamaguchi University, Hospital, Instructor, 医学部・附属病院, 助手 (70294642)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥13,400,000 (Direct Cost: ¥13,400,000)
Fiscal Year 2001: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2000: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 1999: ¥6,300,000 (Direct Cost: ¥6,300,000)
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| Keywords | SIRS / sepsis / Kawasaki disease / monocytes / macrophages / M1 / M2 / Th1 / Th2 / nuclear factor kappa (NF-_KB) / nuclear factor kappa B(NF-κB) / IL-10 / IL-12 / CD14^+CD16^+モノサイト / 成熟マクロファージ / PM2K |
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| Research Abstract |
Recently, sepsis and Kawasaki disease (KD) are identified as systemic response syndrome (SIRS). We investigated the role of peripheral blood monocytes/macrophages in the state of SIRS.
1) We investigated peripheral blood CD14 + CD16 + monocytes subpopulation by flow cytometry, and serum levels of interleukin (IL) -10 and IL -12 using a sandwich enzyme-linked immunosorbent assay. We found that CD14 + CD16 + monocytes were more increased and the serum levels of IL -10, but not IL -12, were higher during acute SIRS than convalescent stage and controls. 2) We also examined peripheral blood monocytes using a monoclonal antibody, PM-2K, which recognizes mature macrophages but not monocytes. Approximately 15-20% of peripheral blood CD14 + monocytes/macrophages from KD patients were positive for PM-2K antibody. Monocytes partly differentiate into macrophages in the peripheral circulation during the acute SIRS. 3) T helper (Th) 1 and Th2 subsets have been implicated in the regulation of many immune responses. We investigated peripheral blood T cells of SIRS, focusing on Th1 and Th2 imbalance, using intracellular cytokine staining and analysis of the cytokine-producing T cells by flow cytometry. We observed a decrease of IFN-γ-producing CD3 + T cells during the acute stage of SIRS. 4) We investigated the activation of transcription factor NF-_KB for genes that encode the proinflammatory cytokines in CD14 + monocytes/macrophages and CD3 + T cells in peripheral blood by means of Western blot and flow cytometric analyses. We found that NF-_KB activation was more increased in CD14 + monocytes/macrophages than in CD3 + T cells in all children during the acute stage.
In conclusion, activation of monocytes/macrophages plays a central role in the pathogenesis of SIRS.
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