Regulation mechanisms of novel cytokine production by metal trace elements
| Project/Area Number |
16K18518
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Functional biochemistry
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| Research Institution | Kanazawa Medical University |
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Principal Investigator |
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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 |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | サイトカイン / 自然免疫 / RNA結合蛋白質 / 蛋白質輸送 / 転写後制御 / 膜蛋白質 / 転写後発現制御 / 生体金属イオン / TLR / Toll様受容体 |
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| Outline of Final Research Achievements |
The regulation of the proinflammatory cytokine production by immune cells is important for the appropriate inflammatory responses. In this study, we focused on the regulation of cytokine secretion in immune cells. We identified Sortilin which is involved in IFN-α secretion in plasmacytoid dendritic cells (pDC), and Sortilin transcripts degraded posttranscriptionally upon stimulation with various TLR ligands. The nucleotide-binding ability of poly-rC-binding proteins, which can act as a trans-acting factor to stabilize Sortilin mRNA, was impaired by zinc ions and alterations of intracellular zinc affect sortilin expression. Poly-rC-binding proteins may posttranscriptionally regulate Sortilin transcripts by sensing intracellular zinc levels.
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| Academic Significance and Societal Importance of the Research Achievements |
免疫細胞から産生される炎症性サイトカインの分泌制御は，適切な炎症応答を保つうえで極めて重要である．本研究では，抗ウイルス免疫に関与する形質細胞様樹状細胞（pDC）において，IFN-α分泌に関わる分子としてSortilinを同定し，その重要性を明らかにした．また，SortilinがTLRシグナル依存的にmRNAレベルで発現制御を受けており，その制御にRNA結合蛋白質であるポリC結合蛋白質が関与している事，更に細胞内の亜鉛がSortilinの制御に関わることを明らかにした．
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Report
(4 results)
Research Products
(19 results)
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[Journal Article] Monomeric Form of Peptidylarginine Deiminase Type I Revealed by X-ray Crystallography and Small-Angle X-ray Scattering.2016
Author(s)
Saijo, S., Nagai, A., Kinjo, S., Mashimo, R., Akimoto, M., Kizawa, K., Yabe-Wada, T., Shimizu, N., Takahara, H., Unno, M.
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Journal Title
J. Mol. Biol.
Volume: 428
Issue: 15
Pages: 3058-3073
DOI
Related Report
Peer Reviewed
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[Presentation] Structural Studies of Peptidylarginine Deiminase Type I using X-ray Crystallography and Small-Angle X-ray Scattering2016
Author(s)
A.Nagai, S.Saijo, S.Kinjo, R.Mashimo, M.Akimoto, K.Kizawa, T.Yabe-Wada, N.Shimizu, H.Takahara, M.Unno
Organizer
The International Symposium of Quantum Beam Science at Ibaraki University
Place of Presentation
Ibaraki University, Mito, JAPAN
Year and Date
2016-11-19
Related Report
Int'l Joint Research
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[Presentation] Structural Studies of Peptidylarginine Deiminase Type I using X-ray Crystallography and Small-angle X-ray Scattering2016
Author(s)
A.Nagai, S.Saijo, S.Kinjo, R.Mashimo, M.Akimoto, K.Kizawa, T.Yabe-Wada, N.Shimizu, H.Takahara, M.Unno
Organizer
14th International Conference of the Asian Crystallographic Association
Place of Presentation
Hanoi University of Science and Technology, Hanoi, Vietnam
Related Report
Int'l Joint Research
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