| Project/Area Number |
16K11439
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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 |
Morphological basic dentistry
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| Research Institution | Niigata University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
寺尾 豊 新潟大学, 医歯学系, 教授 (50397717)
小田 真隆 京都薬科大学, 薬学部, 教授 (00412403)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 肺炎球菌 / ニューモリシン / 好中球エラスターゼ / 肺炎 / 誤嚥性肺炎 |
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| Outline of Final Research Achievements |
Bacterial pneumonia constitutes a leading cause of morbidity and mortality worldwide, being responsible for approximately 3.5 million deaths annually. In this study, we showed that pneumococcal autolysis induces pneumolysin release, which exerts cytotoxicity against infiltrating neutrophils. However, we also observed that pneumolysin exhibited less cytotoxicity against alveolar epithelial cells and macrophages. Therefore, S. pneumoniae exploits NE leakage from degraded neutrophils to promote alveolar epithelial cell injury. We also demonstrated that NE cleaves Toll-like receptors and inflammatory cytokines. Our work indicates that NE induced by S. pneumoniae subverts the innate immune response and that inhibition of this enzyme may constitute a novel therapeutic option for the treatment of pneumococcal pneumonia.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は，病原細菌（肺炎球菌）が感染した宿主よりプロテアーゼを誘導して，間接的に肺の免疫機構を崩壊させることを明らかにした点において，学術的意義が高い．肺炎球菌は近年薬剤耐性化の進行が問題になっているが，プロテアーゼ阻害剤の開発により薬剤耐性の有無に関わらず肺炎治療に結びつけることが可能であることも示唆された．肺炎をを軽症化・治療補助する薬剤開発の提案ができれば，数千億円の波及効果が推計されており，社会的意義も高い．
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