| Project/Area Number |
26461481
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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 | Fukushima Medical University (2016-2017)
Department of Clinical Research, National Hospital Organization Nagasaki Medical Center (2014-2015) |
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Principal Investigator |
Migita Kiyoshi 福島県立医科大学, 医学部, 教授 (60264214)
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| Co-Investigator(Kenkyū-buntansha) |
増本 純也 愛媛大学, プロテオサイエンスセンター, 教授 (20334914)
川上 純 長崎大学, 医歯薬学総合研究科(医学系), 教授 (90325639)
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| Project Period (FY) |
2014-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | IL-1 / インフラマソーム / 好中球 / TNF-α / カスパーゼ1 / NOD様受容体 / サイトカインネットワーク / 血清アミロイド |
|---|
| Outline of Final Research Achievements |
We investigated the proinflammatory effects of SAA in vitro in relation to the NLRP3 inflammasome in neutrophils. SAA stimulation induced pro-IL-1β mRNA expression in neutrophils. Furthermore, SAA engaged the caspase-1-activating inflammasome, resulting in the production of active IL-1β. SAA-induced pro-IL-1β expression was marginally suppressed by the Syk specific inhibitor, R406, and SAA-induced pro-IL-1β processing in neutrophils was prevented by R406. Furthermore, SAA-induced NLRP3 mRNA expression was completely blocked by R406. Analysis of intracellular signaling revealed that SAA stimulation activated the tyrosine kinase Syk and mitogen-activated protein kinase (MAPK). These results demonstrate that the innate neutrophil immune response against SAA involves a two-step activation process: an initial signal promoting expression of pro-IL-1β and a second signal involving Syk-dependent activation of the NLRP3 inflammasome, allowing processing of pro-IL-1β.
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