NETs including oxidative mitochondria DNA might make worse the autoimmune-inflammation in CGD
| Project/Area Number |
17K10006
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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 |
Collagenous pathology/Allergology
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| Research Institution | Kitasato University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
大津 真 東京大学, 医科学研究所, 准教授 (30361330)
竹内 康雄 北里大学, 医学部, 教授 (60286359)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 制御性細胞死 / 好中球 / 慢性肉芽腫症 / NETosis / Apoptosis / ミトコンドリア / 好中球NETosis / 全身性エリテマトーデス / プログラム細胞死 |
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| Outline of Final Research Achievements |
NETosis has been known as neutrophil unique cell death releasing extracellular chromatin structure considered to be implicated in several autoimmune diseases and inflammatory disorders. Activation of NETosis requires ROS production usually dependent on activation of NOX2. We found that U1 RNP, however, could induce NETosis independent on activation of NOX2, involved with mitochondrial ROS production. The addition of U1 RNP could induce Calcium influx in both wild type and NOX2-/- neutrophils. Because the addition of U1 RNP could induce both apoptosis and NETosis. The inhibition of Apoptosis with several caspase inhibitors, accelerate releasing more NETs including mitochondrial-oxidative-DNA, which is known as proinflammatory factor secreting type1 IFN. Our results indicate that the imbalance between Apoptosis and NETosis might make worse the inflammatory disease.
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| Academic Significance and Societal Importance of the Research Achievements |
我々はマウス好中球を用いた新しいNETosis誘導系を構築した。これを用いた解析の結果、NETosisを阻害すると好中球のApoptosisが起こり、Apoptosisを阻害するとNETosisが亢進することが示唆された。生体内においてApoptosisは抗炎症的な細胞死であり、NETosisは炎症誘発的細胞死である。これらは個体が細菌に暴露した時に、さらに炎症細胞を動員するのか、炎症を収束させるのかを制御する一つの要因になっている可能性がある。これらの細胞死バランスへの治療的介入は、有効かもしれないが、長期的にそのインバランスがもたらす副反応を視野に入れて検討すべきであると我々は考える。
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Report
(5 results)
Research Products
(7 results)
