| Project/Area Number |
20K09907
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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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| Review Section |
Basic Section 57020:Oral pathobiological science-related
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| Research Institution | Saga University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 歯周病菌 / 免疫回避 / 治療標的 / 歯周病 / ジンジパイン / Siglec / 感染防御 |
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| Outline of Research at the Start |
既存のジンジパイン阻害剤よりも強力な新規ジンジパイン阻害剤を開発し、それを用いて歯周病菌に対する治療効果を個体レベルで評価することで、「歯周病菌とSiglec5の相互作用による免疫回避機構」を標的とした新規治療戦略の有効性を示す。
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| Outline of Final Research Achievements |
Finding that inhibition of gingipain may be a novel therapeutic strategy against periodontal disease bacteria, we conducted a comprehensive search for gingipain inhibitors and found two peptide-based inhibitors and one small molecule inhibitor. These gingipain inhibitors enhanced the immune response to periodontal disease bacteria by human peripheral blood monocytes and increased the production of IL-8 and TNF. In addition, these gingipain inhibitors promoted neutrophil and monocyte infiltration in the peripheral blood, spleen, and lungs, enhanced TNF and IL-6 expression, and accelerated the clearance rate of periodontal bacteria in each tissue in a systemic infection model of mice.
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| Academic Significance and Societal Importance of the Research Achievements |
歯周病菌はジンジパインを介して宿主免疫応答を抑制しており、ジンジパイン阻害剤は、その免疫抑制を解除することで、宿主免疫応答を増強できることが明らかとなった。これにより、ジンジパイン阻害剤が、歯周病菌に対する新規治療薬として有望である可能性が示唆された。
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