Amelogenin downregulates interferon gamma-induced major histocompatibility complex class II expression in macrophages
| Project/Area Number |
18K17052
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 57030:Conservative dentistry-related
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| Research Institution | Kyushu University |
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Principal Investigator |
Tanaka Urara 九州大学, 大学病院, 助教 (50734993)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 歯周炎 / アメロジェニン / マクロファージ / 抗原提示 / ヒストン修飾 / 炎症 |
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| Outline of Final Research Achievements |
Enamel matrix derivatives (EMDs)-based periodontal tissue regenerative therapy is known to promote healing with minimal inflammatory response after periodontal surgery, i. e., it promotes wound healing with reduced pain and swelling.It has also been reported that macrophages stimulated with amelogenin, a major component of EMD, produce various anti-inflammatory cytokines and growth factors. We previously found that stimulation of monocytes with murine recombinant M180 (rM180) amelogenin suppresses major histocompatibility complex class II (MHC II) gene expression using microarray analysis. However, the detailed molecular mechanisms for this process remain unclear.in this study, we demonstrated that amelogenin suppresses MHC II expression by altering chromatin structure and inhibiting CIITA p-IV transcription activity, and attenuates subsequent T cell activation.
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| Academic Significance and Societal Importance of the Research Achievements |
歯周組織再生療法で臨床応用されているアメロジェニンは抗原提示を抑制することで、Th1細胞による細胞性免疫を中心とした免疫応答の発動を制御し、結果的に外科処置後の創傷治癒を促進させている可能性を見出した。アメロジェニンによる組織再生誘導促進効果の起点は免疫細胞における炎症制御にある可能性が高く、将来的に、アメロジェニンを利用した新規歯周治療薬の開発に資するのみでなく、生体蛋白であるアメロジェニンが臓器移植における拒絶反応の制御を始め、I型糖尿病、多発性硬化症、関節リウマチなどのMHC II関連自己免疫疾患に対する安全な免疫抑制剤として応用できる可能性があることが示唆された。
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Report
(4 results)
Research Products
(9 results)
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[Journal Article] Amelogenin Downregulates Interferon Gamma-Induced Major Histocompatibility Complex Class II Expression Through Suppression of Euchromatin Formation in the Class II Transactivator Promoter IV Region in Macrophages2020
Author(s)
Yotsumoto K, Sanui T, Tanaka U, Yamato H, Alshargabi R, Shinjo T, Nakao Y, Watanabe Y, Hayashi C, Taketomi T, Fukuda T, Nishimura F.
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Journal Title
Frontiers in Immunology
Volume: 11
Pages: 709-709
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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