| Project/Area Number |
22790421
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Bacteriology (including Mycology)
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| Research Institution | National Institute of Health Sciences |
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Principal Investigator |
SUGIYAMA Kei-ichi 国立医薬品食品衛生研究所, 変異遺伝部変異遺伝部, 室長 (80356237)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | TLR / ペプチド / マイコトキシン / 敗血症 |
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| Research Abstract |
Lipopolysaccharide (LPS) is a component of the membrane of Gram-negative bacteria, and a ligand for Toll-like receptor 4 (TLR4). LPS is generally considered to be a dominant pathogenic element in Gram-negative bacterial infection, and can lead to sepsis. Sepsis progresses to severe sepsis and septic shock. Around 750,000 cases of sepsis occur in the United States of America per year, and at least 225,000 of these are lethal. In spite of the high mortality rate, effective drugs to improve the lethality of sepsis have not been created. A peptide (STM28) which inhibited LPS-induced nuclear factor-κB activation in macrophage cells have isolated. In this study, it is revealed that STM28 has no effect on intracellular TLR-mediated signaling pathways. On the other hand, deoxynivalenol, trichothecene mycotoxin, inhibits the LPS-induced nitric oxide and interferon- β production. The present study also shows that this toxin inhibits MyD88-dependent pathway via TLR4. Moreover, I found that citrinin, which is a mycotoxin, down-regulates LPS signaling. These results suggest that STM28 and these toxins may have utility as a novel therapeutic agent for bacterial sepsis.
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