| Project/Area Number |
17K08393
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Environmental and hygienic pharmacy
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| Research Institution | Josai University (2019)
Hoshi University (2017-2018) |
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Principal Investigator |
Tsuji Tsutomu 城西大学, 薬学部, 客員教授 (00143503)
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| Co-Investigator(Kenkyū-buntansha) |
奥 輝明 星薬科大学, 薬学部, 講師 (20409361)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | マクロファージ / 血小板 / エンドトキシン / 炎症性サイトカイン / 一酸化窒素 / NF-κB / 免疫調節 / 腫瘍壊死因子 / インターロイキン6 / NO合成酵素 / アルギナーゼ / サイトカイン |
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| Outline of Final Research Achievements |
Susceptibility of macrophages to bacterial endotoxin was reduced in the presence of platelets or proteins derived from platelets, and these cells produced lowered levels of nitric oxide (NO) and inflammatory cytokines. The suppression of these macrophage functions was found to involve the negative regulation of the NF-κB signaling pathway; especially increased expression of nitric oxide synthase and decreased expression of arginase in relation to the suppression of NO synthesis. Furthermore, we attempted to develop novel sensitive methods for the evaluation of macrophage susceptibility to endotoxin. We have developed two methods, in which we utilized differentiated human monocytic cells or a reporter cell line containing NF-κB-responsive elements.
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| Academic Significance and Societal Importance of the Research Achievements |
細菌感染に伴うエンドトキシン（内毒素）ショックは，しばしば多臓器障害などの重篤な結果を招く．この過程にはマクロファージの過剰な活性化により産生されるサイトカインや炎症性メディエーターが深く関与する．本研究の成果は，血小板または血小板由来の物質によってマクロファージ機能の活性化が抑制されることを見出し，エンドトキシンショックの緩和及び重篤化予防などに貢献するものと思われる．また，本研究で開発したエンドトキシン感受性の高感度，短時間測定法は，創薬研究などの薬学的応用が期待される．
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