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Comparative survey of endogenous and environmental factors that activate autoinflammatory disease responsible gene products in Turkey and Japan

Research Project

Project/Area Number 17H04656
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section海外学術
Research Field Hygiene and public health
Research InstitutionEhime University

Principal Investigator

MASUMOTO JUNYA  愛媛大学, プロテオサイエンスセンター, 教授 (20334914)

Co-Investigator(Kenkyū-buntansha) 谷内江 昭宏  金沢大学, 附属病院, 特任教授 (40210281)
竹田 浩之  愛媛大学, プロテオサイエンスセンター, 准教授 (40609393)
澤崎 達也  愛媛大学, プロテオサイエンスセンター, 教授 (50314969)
上松 一永  信州大学, 医学部, 委嘱講師 (60262721)
右田 清志  福島県立医科大学, 医学部, 教授 (60264214)
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) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2019: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2017: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Keywords自己炎症疾患 / インフラマソーム / トルコ / 環境因子 / 家族性地中海熱 / 発症トリガー / 無細胞系
Outline of Final Research Achievements

We found that there is a specific pattern of serum cytokine levels in patients with familial Mediterranean fever. In particular, since the importance of IL-6, IL-17, and IL-18 was suggested, the pyrin inflammasome may be important for the activation of IL-18, but not IL-1β. Using the cell-free inflammasome reconstitution system, we studied for endogenous ligands that promote inflammasome formation in a cell-free inflammsome. As a result, we found that islet amyloid polypeptide (IAPP) and beta amyloid (Aβ) interact with inflammasome directly. On the other hand, we found that pyrin interacts with another amyloid different from IAPP and Aβ.

Academic Significance and Societal Importance of the Research Achievements

AβやIAPPとは異なるアミロイドがpyrinインフラマソームの形成を促進することが明らかになった。トルコ周辺では宗教上の理由から、絶食期間が一定の割合で生活習慣の一部になっているケースが多く、この期間に内因性アミロイドが増加すると考えられる。自己炎症疾患の発作の予防には、規則正しい食生活と睡眠によって、血中のアミロイドの増加を抑えることが考えられるが、診断と治療への応用については、さらなる解析が必要である。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (31 results)

All 2019 2018 2017 Other

All Int'l Joint Research (2 results) Journal Article (14 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 14 results,  Open Access: 10 results,  Acknowledgement Compliant: 2 results) Presentation (13 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] Bogazici大学/Marmara 大学/Istanbul大学(トルコ)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Bogazici大学/Marmara 大学/Istanbul 大学(トルコ)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Valve Interstitial Cell-Specific Cyclooxygenase-1 Associated With Calcification of Aortic Valves.2019

    • Author(s)
      Sakaue T, Hamaguchi M, Aono J, Nakashiro KI, Shikata F, Kawakami N, Oshima Y, Kurata M,?Nanba D, Masumoto J, Yamaguchi O, Higashiyama S, Izutani H.
    • Journal Title

      Ann Thorac Surg

      Volume: S0003-4975 Issue: 1 Pages: 31717-5

    • DOI

      10.1016/j.athoracsur.2019.09.085

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A simple mouse model of pericardial adhesions2019

    • Author(s)
      Kojima Ai、Sakaue Tomohisa、Okazaki Mikio、Shikata Fumiaki、Kurata Mie、Imai Yuuki、Nakaoka Hirotomo、Masumoto Junya、Uchita Shunji、Izutani Hironori
    • Journal Title

      Journal of Cardiothoracic Surgery

      Volume: 14 Issue: 1 Pages: 124-124

    • DOI

      10.1186/s13019-019-0940-9

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genomic analysis of Hepatitis B virus and its association with disease manifestations in Bangladesh2019

    • Author(s)
      Raihan Ruksana、Akbar Sheikh Mohammad Fazle、Al Mahtab Mamun、Takahashi Kazuaki、Masumoto Junya、Tabassum Shahina、Tee Kok Keng、Binti Mohamed Rosmawati
    • Journal Title

      PLOS ONE

      Volume: 14 Issue: 6 Pages: e0218744-e0218744

    • DOI

      10.1371/journal.pone.0218744

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The role of interleukin-1 in general pathology2019

    • Author(s)
      Kaneko N, Kurata M, Yamamoto T, Morikawa S, Masumoto J.
    • Journal Title

      Inflammation and Regeneration

      Volume: 印刷中 Issue: 1 Pages: 12-12

    • DOI

      10.1186/s41232-019-0101-5

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical features and new diagnostic criteria for the syndrome of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis2019

    • Author(s)
      Takeuchi Yusuke、Shigemura Tomonari、Kobayashi Norimoto、Nagumo Haruo、Furumoto Masahiro、Ogasawara Kyo、Fujii Hitomi、Takizawa Masahiro、Soga Takashi、Matoba Hisanori、Masumoto Junya、Fukushima Keitaro、Migita Kiyoshi、Ojima Toshiyuki、Umeda Yoh、Agematsu Kazunaga
    • Journal Title

      International Journal of Rheumatic Diseases

      Volume: 22 Issue: 8 Pages: 1489-1497

    • DOI

      10.1111/1756-185x.13610

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical features and new diagnostic criteria of the syndrome of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA)2019

    • Author(s)
      Takeuchi Y, Shigemura T, Kobayashi N, Nagumo H, Furumoto M, Ogasawara K, Fujii H, Takizawa M, Soga T, Matoba H, Masumoto J, Fukushima K, Migita K, Ojima T, Umeda Y, AgematsuK.
    • Journal Title

      International Journal of Rheumatic Diseases

      Volume: in press

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Amyloid β directly interacts with NLRP3 to initiate inflammasome activation: identification of an intrinsic NLRP3 ligand in a cell-free system2018

    • Author(s)
      Nakanishi Ayaka、Kaneko Naoe、Takeda Hiroyuki、Sawasaki Tatsuya、Morikawa Shinnosuke、Zhou Wei、Kurata Mie、Yamamoto Toshihiro、Akbar Sheikh Mohammad Fazle、Zako Tamotsu、Masumoto Junya
    • Journal Title

      Inflammation and Regeneration

      Volume: 38 Issue: 1 Pages: 27-27

    • DOI

      10.1186/s41232-018-0085-6

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Musculoskeletal manifestations occur predominantly in patients with later-onset familial Mediterranean fever: Data from a multicenter, prospective national cohort study in Japan.2018

    • Author(s)
      Endo Y, Koga T, Ishida M, Fujita Y, Tsuji S, Takatani A, Shimizu T, Sumiyoshi R, Igawa T, Umeda M, Fukui S, Nishino A, Kawashiri SY, Iwamoto N, Ichinose K, Tamai M, Nakamura H, Origuchi T, Agematsu K, Yachie A, Masumoto J, Migita K, Kawakami A.
    • Journal Title

      Arthritis Res Ther.

      Volume: 20 Issue: 1 Pages: 257-257

    • DOI

      10.1186/s13075-018-1738-1

    • NAID

      120006987889

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] IAPP/amylin deposition, which is correlated with expressions of ASC and IL-1β in β-cells of Langerhans’ islets, directly initiates NLRP3 inflammasome activation2018

    • Author(s)
      Morikawa S, Kaneko N, Okumura C, Taguchi H, Kurata M, Yamamoto T, Osawa H, Nakanishi A, Zako T, Masumoto J.
    • Journal Title

      International Journal of Immunopathology and Pharmacology

      Volume: 32 Pages: 205873841878874-205873841878874

    • DOI

      10.1177/2058738418788749

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Analysis of biomarker serum levels in IVIG and infliximab refractory Kawasaki disease patients2018

    • Author(s)
      Hachiya A, Kobayashi N, Matsuzaki S, Takeuchi Y, Akazawa Y, Shigemura T, Motoki N, Masumoto J, Agematsu K.
    • Journal Title

      Clinical Rheumatology

      Volume: 37 Issue: 7 Pages: 1937-1943

    • DOI

      10.1007/s10067-017-3952-7

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed
  • [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
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Early diagnosis of early-onset sarcoidosis: a case report with functional analysis and review of the literature.2017

    • Author(s)
      Takeuchi Y, Shigemura T, Kobayashi N, Kaneko N, Iwasaki T, Minami K, Kobayashi K, Matsumoto J, Agematsu K.
    • Journal Title

      Clinical Rheumatology

      Volume: 36 Issue: 5 Pages: 1189-1196

    • DOI

      10.1007/s10067-017-3544-6

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Applications of reconstituted inflammasomes in a cell-free system to drug discovery and elucidation of the pathogenesis of autoinflammatory diseases.2017

    • Author(s)
      Kaneko N, Iwasaki T, Ito Y, Takeda H, Sawasaki T, Morikawa S, Nakano N, Kurata M, Masumoto J.
    • Journal Title

      Inflammation and Regeneration

      Volume: 印刷中 Issue: 1 Pages: 9-9

    • DOI

      10.1186/s41232-017-0040-y

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Poly (I:C) and hyaluronic acid directly interact with NLRP3, resulting in the assembly of NLRP3 and ASC in a cell-free system.2017

    • Author(s)
      Kaneko N, Ito Y, Iwasaki T, Takeda H, Sawasaki T, Migita K, Agematsu K, Koga T, Kawakami A, Yachie A, Yoshiura K, Morikawa S, Kurata M, Masumoto J.
    • Journal Title

      European Journal of Inflammation

      Volume: 印刷中 Issue: 2 Pages: 85-97

    • DOI

      10.1177/1721727x17711047

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] NLRP3インフラマソームを活性化する未知分子の同定2019

    • Author(s)
      増本純也,金子直恵,周薇,竹田浩之,澤崎 達也,山本敏弘,森川紳之祐,倉田美恵
    • Organizer
      第40回日本炎症・再生医学会(神戸)
    • Related Report
      2019 Annual Research Report
  • [Presentation] 家族性地中海熱の精密医療の実現への試み2019

    • Author(s)
      川上純,遠藤友志郎,古賀 智裕,田中 義正,右田 清志,吉浦孝一郎,佐藤俊太朗, 上松 一永,谷内江明宏,増本 純也,浦野健
    • Organizer
      第40回日本炎症・再生医学会(神戸)
    • Related Report
      2019 Annual Research Report
  • [Presentation] 無細胞インフラマソーム再構成系による創薬スクリーニング2019

    • Author(s)
      金子直恵, 竹田浩之, 澤崎達也, 増本純也
    • Organizer
      第92回日本生化学会大会(横浜)
    • Related Report
      2019 Annual Research Report
  • [Presentation] アミロイドとの直接相互作用によるNLRP3インフラマソーム形成の可能性2019

    • Author(s)
      増本純也, 金子直恵, 中西文香, 竹田浩之, 澤崎達也, 座古保, 森川紳之祐
    • Organizer
      第92回日本生化学会大会(横浜)
    • Related Report
      2019 Annual Research Report
  • [Presentation] 増本純也, 金子直恵, 竹田浩之, 澤崎達也, 中西文香, 座古保, 森川紳之祐2019

    • Author(s)
      アミロイドタンパク質との直接相互作用によるNLRP3インフラマソーム形成の可能性
    • Organizer
      第42回日本分子生物学会年会(福岡)
    • Related Report
      2019 Annual Research Report
  • [Presentation] 無細胞NLRP3インフラマソーム再構成系を用いた自己炎症疾患の分子標的薬の開発2019

    • Author(s)
      金子直恵, 重村倫成, 上松一永, 倉田美恵, 竹田浩之, 澤崎達也, 森川紳之祐
    • Organizer
      第42回日本分子生物学会年会(福岡)
    • Related Report
      2019 Annual Research Report
  • [Presentation] Quantitative evaluation of mRNA expression of MEFV gene product pyrin in human tissues2018

    • Author(s)
      Nakano N, Kaneko N, Kurata N, Yamamoto T, Urano T, Koga T, Kawakami A, Yachie A, Agematsu K, Migita K, Yoshiura K, Ishii E, Masumoto J.
    • Organizer
      European Society for Immunodeficiencies 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] インフラマソーム活性化メカニズム解説のための擬人化(キャラクター化)を用いた漫画(マンガ) によるアウトリーチ活動の試み2018

    • Author(s)
      和田有希子, 金子直恵, 増本純也.
    • Organizer
      第41回分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Aβのアミロイド凝集体によるNLRP3インフラマソームの活性化2018

    • Author(s)
      中西文香、金子直恵、座古保、増本純也.
    • Organizer
      第41回分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] アミロイドAβの重合化は試験管内無細胞インフラマソームの形成を促進する2018

    • Author(s)
      金子直恵、中西文香、座古保、増本純也.
    • Organizer
      第39回日本炎症・再生医学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 3.無細胞タンパク質複合体再構成系による自己炎症疾患の病態解明と特異的分子標的治療薬探索2018

    • Author(s)
      増本純也, 金子直恵, 伊藤有紀, 山本敏弘, 倉田美恵, 中野直子, 森川紳之祐, 周薇, 竹田浩之, 澤崎達也
    • Organizer
      第1回日本免疫不全・自己炎症学会総会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 無細胞系によるNLRP3と直接相互作用する内因性物質の同定2017

    • Author(s)
      増本純也, 金子直恵, 伊藤 有紀
    • Organizer
      第38回日本炎症・再生医学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 無細胞系によるNLRP3インフラソームと直接相互作用する物質の探索, 口演2017

    • Author(s)
      増本純也, 金子直恵, 伊藤有紀, 森川紳之祐, 山本敏弘, 倉田美恵
    • Organizer
      ,第12回臨床ストレス応答学会大会, 2017/11/4, 国内
    • Related Report
      2017 Annual Research Report
  • [Remarks] 愛媛大学プロテオサイエンスセンター 病理学部門

    • URL

      http://www.pros.ehime-u.ac.jp/section/09.html

    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] マックル・ウェルズ症候群の治療用医薬組成物2019

    • Inventor(s)
      増本純也、金子直恵、澤崎達也、竹田浩之
    • Industrial Property Rights Holder
      増本純也、金子直恵、澤崎達也、竹田浩之
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-238430
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2022-08-19  

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