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Interleukin-1 targeting therapy using low molecular weight compounds in inflammatory disorder

Research Project

Project/Area Number 26461481
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Collagenous pathology/Allergology
Research InstitutionFukushima 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)
KeywordsIL-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.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (4 results)

All 2017 2016 2015

All Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 4 results,  Acknowledgement Compliant: 2 results)

  • [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
    • Journal Title

      Rheumatology

      Volume: 57 Issue: 4 Pages: 718-726

    • DOI

      10.1093/rheumatology/kex451

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comparison of serum inflammatory cytokine concentrations in familial Mediterranean fever and rheumatoid arthritis patients2017

    • Author(s)
      Koga T、Kawashiri S-y、Migita K、Sato S、Umeda M、Fukui S、Nishino A、Nonaka F、Iwamoto N、Ichinose K、Tamai M、Nakamura H、Origuchi T、Ueki Y、Masumoto J、Agematsu K、Yachie A、Eguchi K、Kawakami A
    • Journal Title

      Scandinavian Journal of Rheumatology

      Volume: - Issue: 4 Pages: 1-3

    • DOI

      10.1080/03009742.2017.1363281

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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.
    • Journal Title

      Arthritis Res Ther.

      Volume: 18 Issue: 1 Pages: 175-175

    • DOI

      10.1186/s13075-016-1071-5

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [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.
    • Journal Title

      PLoS One

      Volume: 10 Issue: 11 Pages: e0136908-e0136908

    • DOI

      10.1371/journal.pone.0136908

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant

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Published: 2014-04-04   Modified: 2019-03-29  

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