Crosstalk of Gingival Fibroblasts and Macrophages in Inflammatory Cytokine Cascade: Potential Mechanisms of Periodontitis with Diabetes.
| Project/Area Number |
16K11832
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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 |
Periodontology
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| Research Institution | The University of Tokushima |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
木戸 淳一 徳島大学, 大学院医歯薬学研究部(歯学域), 准教授 (10195315)
梶浦 由加里 徳島大学, 大学院医歯薬学研究部(歯学系), 特任助教 (40758869)
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 糖尿病関連歯周炎 / 歯肉線維芽細胞 / マクロファージ / 糖尿病性歯周炎 / 糖尿病 / 歯周病 / IL-6 / カルプロテクチン / 歯学 / 歯周病態 |
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| Outline of Final Research Achievements |
Aim of this study was to explore the biological pathogenesis of severe periodontitis in diabetic patients focusing on the crosstalk of human gingival fibroblasts (HGFs) and macrophages. Results are shown as below: There were statistical correlation between IL-1β and sIL-6R levels in GCF and HbA1c in periodontitis patients with DM. HG and CPT significantly induced sIL-6R production in THP-1 macrophages. HG significantly enhanced IL-1β or IL-6/sIL-6R-induced MMP-1 production in HGFs. Finally, MMP-1 production in HGFs cultured with HG increased significantly by CM from THP-1 macrophages cultured with HG. The induction of MMP-1 by the CM from THP-1 macrophages cultured with HG was significantly inhibited by dose dependent of IL-1ra in HGFs cultured with HG. In conclusion, diabetic conditions such as HG induce IL-1β and sIL-6R production from macrophages in inflammatory periodontal tissues and may exacerbate the periodontitis synergistically via MMP-1 production from HGFs.
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| Academic Significance and Societal Importance of the Research Achievements |
「IL-6は歯周病の重症化機序の重要な因子である」という長年の研究成果を基盤にして，高グルコースとカルプロテクチンを基点としたIL-6動態の相乗的な増強効果を想定し，糖尿病関連歯周炎の重症化機序の一端を解明できた。また，歯肉線維芽細胞による歯周組織破壊機序を標的にした研究ではなく，その上流で繰り広げられるIL-6とsIL-6Rの産生機序に着目し，歯肉線維芽細胞と歯周組織に浸潤したマクロファージとの細胞クロストークに焦点を当てた点は独創的であり，本研究によってIL-6動態に着目した糖尿病関連歯周炎の重症化機序が明らかになり，将来，本領域疾患の創薬技術の発展に貢献し得ると期待できる。
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Report
(4 results)
Research Products
(14 results)
