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Establishment of a method of IL-18 inhibitor based on a new molecular mechanism

Research Project

Project/Area Number 16K10025
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionGifu University

Principal Investigator

Kato Zenichiro  岐阜大学, 大学院医学系研究科, 教授 (90303502)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsIL-18 / 阻害薬 / 阻害剤 / 立体構造
Outline of Final Research Achievements

We performed analyses of the molecular mechanism by IL-18 inhibitor. In addition to the cutokine inhibition experiments, the molecular interaction analysis was done in atomic resolution. Especially, the atomic interactions between IL-18 ligand and the innate inihibitory peptide were precisely determined by using nuclear magnetic resonance technique. Using the above biological and molecular information, further improvement of the inhibitor should be feasible.

Academic Significance and Societal Importance of the Research Achievements

病気に関与する分子をそれぞれ単にひとつの点として考えるのではなく、ナノメーター以下の原子レベルでの分子構造をもとに病態解析及びその治療法の開発を行うものであり、詳細な構造を決定したことにより、単なるランダムスクリーニングではなく、立体構造に基づいた論理的な蛋白工学的機能分子デザイン・開発が可能となった。本研究にて開発される治療分子を得ることは、免疫システムのkey modulatorを自在に調節可能となる事に繋がり、アレルギーのみならず、リウマチ性疾患や多発性硬化症などの神経難病を含む自己免疫異常に対しても有効な手段の一つとなり、対象となるポピュレーションは大きい。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (3 results)

All 2019 2017 2016

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 3 results)

  • [Journal Article] An innate interaction between IL-18 and the propeptide that inactivates its precursor form2019

    • Author(s)
      Naotaka Tsutsumi, Ayumi Yokota, Takeshi Kimura, Zenichiro Kato, Toshiyuki Fukao, Masahiro Shirakawa, Hidenori Ohnishi & Hidehito Tochio
    • Journal Title

      Scientific Reportsvolume

      Volume: 9 Issue: 1 Pages: 6160-6160

    • DOI

      10.1038/s41598-019-42661-5

    • NAID

      120007006235

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Outbreak of immediate-type hydrolyzed wheat protein allergy due to a facial soap in Japan.2017

    • Author(s)
      Yagami A, Aihara M, Ikezawa Z, Hide M, Kishikawa R, Morita E, Chinuki Y, Fukutomi Y, Urisu A, Fukushima A, Itagaki Y, Sugiura SI, Tanaka H, Teshima R, Kato Z, Noguchi E, Nakamura M, Saito H, Matsunaga K.
    • Journal Title

      J Allergy Clin Immunol.

      Volume: 140 Issue: 3 Pages: 879-881

    • DOI

      10.1016/j.jaci.2017.03.019

    • NAID

      120007134447

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Alanine-scanning mutagenesis of human signal transducer and activator of transcription 1 to estimate loss- or gain-of-function variants2016

    • Author(s)
      Kagawa R, Fujiki R, Tsumura M, Sakata S, Nishimura S,Itan Y, Kong XF, Kato Z, Ohnishi H, Hirata O, Saito S, Ikeda M,Baghdadi JE, Bousfiha A, Fujiwara K, Oleastro M, Yancoski J,Perez L, Danielian S, Ailal F, Takada H, Hara T, Anne Puel A, Boisson-Dupuis S, Bustamante J, Casanova JL, Ohara O, Okada S, Masao Kobayashi M.
    • Journal Title

      J Allergy Clin Immunol.

      Volume: - Issue: 1 Pages: 232-241

    • DOI

      10.1016/j.jaci.2016.09.035

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research

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Published: 2016-04-21   Modified: 2020-03-30  

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