USP10 in LPS-stimulated macrophages acts on Regnase-1 to suppress inflammatory cytokines.
| Project/Area Number |
17K08795
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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 |
Experimental pathology
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| Research Institution | Niigata University of Health and Welfare |
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Principal Investigator |
KAWAMURA Hiroki 新潟医療福祉大学, 医療技術学部, 准教授 (20333495)
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| Co-Investigator(Kenkyū-buntansha) |
樋口 雅也 金沢医科大学, 医学部, 教授 (50334678)
高橋 雅彦 新潟大学, 医歯学系, 准教授 (80377192)
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| Project Period (FY) |
2017-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | マクロファージ / USP10 / 炎症性サイトカイン / LPS / IL-6 / IL-1β / TNFα / IL-1 / NF-κB / 炎症 / サイトカイン / 炎症性腸疾患 / 免疫学 / シグナル伝達 |
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| Outline of Final Research Achievements |
This study examined the effect of USP10 on inflammatory cytokine production in macrophages. Stimulation of USP10-KD J774 cells with the TLR4 ligand LPS resulted in decreased proliferative capacity compared to Ren J774 cells, while TNFα, IL-6 and MIP-2 (CXCL2) were significantly increased, and additional stimulation with Nigericn significantly increased IL-1β.These increases in proinflammatory cytokine production capacity were different with TLR2 ligand stimulation and were specific to TLR4 stimulation.This inflammatory response differs from previously reported pathways in which USP10 suppresses NFκ-B activity, suggesting that USP10 affects inflammatory cytokine production through its involvement in the regulation of mRNA levels by Regnase-1. This is a new observation of the inflammatory response, but the pathway of involvement of USP10 in Regnase-1 needs to be clarified. We will further continue this study to contribute to the treatment of inflammatory bowel disease in the future.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、USP10は細胞の種類だけでなく刺激の種類によってIKKλ/NEMOに作用してNF-κB活性を抑制する機能やRegnase-1に作用して炎症性サイトカインの産生を調整する機能など多様な面を持っていることが明らかになった。本研究は当初の仮説と異なる結果となったが、マクロファージにおいてUSP10がRegnase-1のmRNAの量の調節機構に関与することで、炎症性サイトカイン産生に影響を与えることを示唆することができた。これは炎症反応の新しい知見で、各刺激でのUSP10の機能を整理すれば将来的には炎症性腸疾患の治療に貢献できる可能性がある。
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Report
(6 results)
Research Products
(1 results)
