Interleukin-1 targeting therapy using low molecular weight compounds in inflammatory disorder
Project/Area Number |
26461481
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
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) |
Principal Investigator |
Migita Kiyoshi 福島県立医科大学, 医学部, 教授 (60264214)
|
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)
|
Project Period (FY) |
2014-04-01 – 2018-03-31
|
Project Status |
Completed (Fiscal Year 2017)
|
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)
|
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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Report
(5 results)
Research Products
(4 results)
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[Journal Article] MicroRNA-204-3p inhibits lipopolysaccharide-induced cytokines in familial Mediterranean fever via the phosphoinositide 3-kinase γ pathway2017
Author(s)
Koga Tomohiro,Migita Kiyoshi,Sato Tomohito,Sato Shuntaro,Umeda Masataka,Nonaka Fumiaki,Fukui Shoichi,Kawashiri Shin-ya,Iwamoto Naoki,Ichinose Kunihiro,Tamai Mami,Nakamura Hideki,Origuchi Tomoki,Ueki Yukitaka,Masumoto Junya,Agematsu Kazunaga,Yachie Akihiro,Yoshiura Koh-ichiro,Eguchi Katsumi,Kawakami Atsushi
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Journal Title
Rheumatology
Volume: 57
Issue: 4
Pages: 718-726
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Familial Mediterranean fever is no longer a rare disease in Japan.2016
Author(s)
Migita K, Izumi Y, Jiuchi Y, Iwanaga N, Kawahara C, Agematsu K, Yachie A, Masumoto J, Fujikawa K, Yamasaki S, Nakamura T, Ubara Y, Koga T, Nakashima Y, Shimizu T, Umeda M, Nonaka F, Yasunami M, Eguchi K, Yoshiura K, Kawakami A.
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Journal Title
Arthritis Res Ther.
Volume: 18
Issue: 1
Pages: 175-175
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Circulating microRNA Profiles in Patients with Type-1 Autoimmune Hepatitis.2015
Author(s)
Migita K, Komori A, Kozuru H, Jiuchi Y, Nakamura M, Yasunami M, Furukawa H, Abiru S, Yamasaki K, Nagaoka S, Hashimoto S, Bekki S, Kamitsukasa H, Nakamura Y, Ohta H, Shimada M, Takahashi H, et al.
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Journal Title
PLoS One
Volume: 10
Issue: 11
Pages: e0136908-e0136908
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant