1990 Fiscal Year Final Research Report Summary
Structural Analysis and Mechanisms of Action of Various Inflammatory Cytokines
| Project/Area Number |
63440085
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
物質生物化学
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| Research Institution | The University of Tokyo |
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Principal Investigator |
OSAWA Toshiaki Univ. of Tokyo, Fac. of Pharm. Sci., Professor, 薬学部, 教授 (40012603)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Kazuo Univ. of Tokyo, Fac. of Pharm. Sci., Research Associate, 薬学部, 助手 (20174782)
TOYOSHIMA Satoshi Univ. of Tokyo, Fac. of Pharm. Sci., Associat Professor, 薬学部, 助教授 (40092283)
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| Project Period (FY) |
1988 – 1990
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| Keywords | lymphokine / macrophage activating factor / macrophage migration inhibitory factor / lymphotoxin / tumor necrosis factor / interleukin-2 / natural killer cell activating factor |
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| Research Abstract |
1. Purification and structural analysis of inflammatory cytokines
(a) Macrophage chemotactic factor : We purified a low molecular weight peptide having strong macrophage chemotactic activity and elucidated its amino acid sequence. Furthermore, we synthesized this peptide and observed that the synthetic peptide also has strong macrophage chemotactic activity.
(b) Macrophage migration inhibitory factor (MIF) : We purified two kinds of MIF form the culture supernatant of human T cell hybridomas. We elucidated partial amino acid sequences of these two factors and found that these factors are novel lymphokines.
(c) Macrophage activation factor for tumoricidal activity (MAF-C) : We purified MAF-C from the culture supernatant of human T cell hybridomas. Macrophage activating activity of the purified factor was completely inhibited by the addition of anti-IL-2 antibody, suggesting that MAF-C is actually IL-2 or an antigenically related substance with IL-2. Then, we analyzed macrophage activating of recombinant IL-2.
2. Mechanism of action of tumor necrosis factor
We found that activated macrophages kill tumor cells in vivo which are resistant to tumor necrosis factor in vitro. Therefore, we analyzed the mechanism of tumoricidal activity of activated macrophages, and we found that NO produced by activated macrophages depending on the presence of arginine syn ergistically acts on tumor cells with tumor necrosis factor.
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