| Project/Area Number |
23590519
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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 |
Bacteriology (including Mycology)
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| Research Institution | Juntendo University |
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Principal Investigator |
NAGAOKA Isao 順天堂大学, 医学(系)研究科(研究院), 教授 (60164399)
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| Co-Investigator(Kenkyū-buntansha) |
IBA Toshiaki 順天堂大学, 医学部, 教授 (40193635)
KUWAHARA Kyoko 順天堂大学, 医学部, 准教授 (10167976)
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| Co-Investigator(Renkei-kenkyūsha) |
SUZUKI Kaori 順天堂大学, 医学部, 助教 (90631929)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 敗血症 / alrmin / ピロトーシス / 抗菌ペプチド / マクロファージ / 細胞死 / エンドトキシン / カスパーゼ / alarmin |
|---|
| Research Abstract |
Pyroptosis is a caspase-1 dependent cell death, associated with proinflammatory cytokine production, and plays a crucial role in sepsis. Pyroptosis is induced by microbial PAMPs and endogenous DAMPs. Notably, human antimicrobial peptide LL-37 protects the septic animal models. Thus, to elucidate the action of LL-37 on sepsis, we utilized LPS (lipopolysaccharide) and ATP as a PAMP and a DAMP, respectively. The data indicated that the LPS/ATP-treatment of macrophage-like J774 cell induces the features of pyroptosis (IL-1 mRNA expression, caspase-1 activation, inflammasome formation and cell death). Moreover, LL-37 inhibits the LPS/ATP-induced IL-1 expression, caspase-1 activation, inflammasome formation and cell death. Notably, LL-37 suppressed the LPS binding to target cells and ATP-induced/P2X7-mediated caspase-1 activation. These observations suggest that LL-37 potently inhibits the LPS/ATP-induced pyroptosis by blocking the action of LPS and inhibiting the response of P2X7 to ATP.
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