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The chemical biology of low side effects compound in anti-fever drugs, which is derived from the analysis about fatal function by diclofenac.

Research Project

Project/Area Number 20611013
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Chemical biology
Research InstitutionThe University of Tokushima

Principal Investigator

YANO Mihiro (2010)  The University of Tokushima, 疾患酵素学研究センター, 准教授 (40304555)

ユースフ シセ (2008-2009)  The University of Tokushima, 疾患酵素学研究センター, 科学技術振興研究員 (80437649)

Co-Investigator(Kenkyū-buntansha) KIDO Hiroshi  徳島大学, 疾患酵素学研究センター, 教授 (50144978)
矢野 仁康  徳島大学, 疾患酵素学研究センター, 准教授 (40304555)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsインフルエンザウイルス / ジクロフェナクナトリウム / ウイルス放出障害 / インフルエンザ脳症 / 解熱剤 / ジクロフェナック / ウイルス放出阻害 / Caチャネルブロッカー / Naチャネルブロッカー / ライ症候群
Research Abstract

To clarify the mechanisms of influenza encephalitis induced by diclofenac, we examined the effect of influenza virus and diclofenac on the disruption of tight junction (TJ) in human vascular endothelial cells in vitro. In this study, we found that influenza virus induced the degradation of TJ proteins, such as ZO1, leading to its disruption. On the other hands, diclofenac by itself inhibited the synthesis of TJ proteins, consequently accelerating the disruption of TJ induced by influenza infection in vascular endothelial cells.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (33 results)

All 2011 2010 2009 2008 Other

All Journal Article (22 results) (of which Peer Reviewed: 20 results) Presentation (11 results)

  • [Journal Article] Up-regulation of ectopic trypsins in the myocardium by influenza A virus infection triggers acute myocarditis.2011

    • Author(s)
      H-Y Pan, H Yamada, J Chida, S Wang , M Yano, M Yao, H Kido.
    • Journal Title

      Cardiovascular Research. 89(3)

      Pages: 595-603

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effect of inhibitor of Toll-like receptors, protease-activated receptor-2 signaling and trypsin on influenza A virus replication and upregulation of cellular factors in cardiomyocytes.2011

    • Author(s)
      H-Y Pan, M Yano, H Kido.
    • Journal Title

      The Journal of Medical Investigation 58,1,2

      Pages: 19-28

    • NAID

      130004465241

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Up-regulation of ectopic trypsins in the myocardium by influenza A virus infection triggers acute myocarditis2011

    • Author(s)
      H-Y Pan, et al.
    • Journal Title

      Cardiovascular Research

      Volume: 89 Pages: 595-603

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of inhibitor of Toll-like receptors, protease-activated receptor-2 signaling and trypsin on influenza A virus replication and upregulation of cellular factors in cardiomyocytes2011

    • Author(s)
      H-Y Pan, et al.
    • Journal Title

      The Journal of Medical Investigation

      Volume: 58 Pages: 19-28

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Influenza Virus-Cytokine-Protease Cycle in the Pathogenesis of Vascular Hyperpermeability in Severe Influenza.2010

    • Author(s)
      S Wang, TQ Le, N Kurihara, J Chida, Y Cisse, M Yano, H Kido.
    • Journal Title

      Journal of Infectious Disease 202,7

      Pages: 991-1001

    • Related Report
      2010 Final Research Report
  • [Journal Article] Novel Type II Transmembrane Serine Proteases, MSPL and TMPRSS 13, Proteolytically Activate Membrane Fusion Activity of the Hemagglutinin of Highly Pathogenic Avian Influenza Viruses and Induce Their Multicycle Replication.2010

    • Author(s)
      Y Okumura, E Takahashi, M Yano, M Ohuchi, T Daidoji, T Nakaya, W Gaten, HD Klenk, H Kido.
    • Journal Title

      Journal of Virology 84,10

      Pages: 5089-5096

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mechanisms of matrix metalloproteinase-9 upregulation and tissue destruction in various organs in influenza A virus infection.2010

    • Author(s)
      S Wang, T Quang Le, J Chida, Y Cisse, M Yano, H Kido.
    • Journal Title

      J Med Investigation. 57,1,2

      Pages: 26-34

    • NAID

      130004465198

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Rat model of influenza-associated encephalopathy (IAE) : studies of electroencephalogram (EEG) in vivo. Neuroscience.2010

    • Author(s)
      Cisse Y, Wang S, Inoue I, Kido H.
    • Journal Title

      Microbes Infect. 165(4),12(10)

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Influenza virus-cytokine-Protease cycle in the pathogenesis of vascular hyperpermeability in severe influenza2010

    • Author(s)
      S Wang, et al.
    • Journal Title

      The Journal of Infectious Disease

      Volume: 202 Pages: 991-1001

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel type II transmembrane serine protease, MSPL and TMPRSS13, proteolytically activate membrane fusion activation of hemagglutinin of highly pathogenic avian influenza viruses and induce their multicycle replication.2010

    • Author(s)
      Yuushi Okumura
    • Journal Title

      The Journal Virology 84

      Pages: 5089-5096

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Influenza virus-cytokine-protease cycle in the pathogenesis of vascular hyperpermeability in severe influenza.2010

    • Author(s)
      Siye Wang
    • Journal Title

      Journal of Infectious Diseases (In press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanisms of matrix metalloprotease-9 upregulation and tissue destruction in various organs in influenza A virus infection.2010

    • Author(s)
      Siye Wang
    • Journal Title

      J.Med.Invest. 57(1,2)

      Pages: 26-34

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rat model of influenza-associated encephalopathy (IAE) : stidies of electroencephalogram (EEG) in vivo.2010

    • Author(s)
      Youssouf Cisse
    • Journal Title

      Neuroscience 165

      Pages: 1127-1137

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Boost of mucosal secretory immunoglobulin A response by clarithromycin in paediatric influenza.2009

    • Author(s)
      Sawabuchi T, Suzuki S, Iwase K, Ito C, Mizuno D, Togari H, Watanabe I, Talukder SR, Chida J, Kido H.
    • Journal Title

      Respirology. 14(8)

      Pages: 1173-1179

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Host envelope glycoprotein processing proteases are indispensable for entry into human cells by seasonal and highly pathogenic avian influenza viruses.2009

    • Author(s)
      H Kido, Y Okumura, E Takahashi, H-Y Pan, S Wang, T Quang Le, M Yano.
    • Journal Title

      J Mol and Gene Med 3,1

      Pages: 167-175

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Influenza vaccine with Surfacten, a modified pulmonary surfactant, induces systemic and mucosal immune responses without side effects in minipigs.2009

    • Author(s)
      Nishino M, Mizuno D, Kimoto T, Shinahara W, Fukuta A, Takei T, Sumida K, Kitamura S, Shiota H, Kido H.
    • Journal Title

      Vacctine. 18;27(41)

      Pages: 5620-5627

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cleavage of the SARS coronavirus spike glycoprotein by airway proteases enhances virus entry into human bronchial epithelial cells in vitro.2009

    • Author(s)
      Yiu-Wing Kam
    • Journal Title

      PLoS One 4(11)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Boost of mucosal secretoty immunoglobulin A response by clarithromycin in paediatric influenza.2009

    • Author(s)
      Takako Sawabuchi
    • Journal Title

      Respirology 14(8)

      Pages: 1173-1179

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Influenza vaccine with Surfacten, a modified pulmonary surfactant, induces systemic and mucosal immune responses without side effects in minipigs.2009

    • Author(s)
      Maki Nishino
    • Journal Title

      Vaccine 27

      Pages: 5620-5627

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Host envelope glycoprotein processing proteases are indispensable for entry into human cells by seasonal and highly pathogenic avian influenza viruses.2009

    • Author(s)
      Hiroshi Kido
    • Journal Title

      J.Mol.Genet.Med. 3(1)

      Pages: 165-175

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Thermal instability of compound variants of carnitine palmitoyltransferase II and impaired mitochondria1 fuelutilization in influenza-associated encephalopathy.2008

    • Author(s)
      Yao D
    • Journal Title

      Human Mutation 29(5)

      Pages: 718-727

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Attenuation of inducible respiratory immune responses by oseltamivir treatment in mice infected with influenza A virus.

    • Author(s)
      Takahashi E, Kataoka K, Fujii K, Chida J, Mizuno D, Fukui M, Hiro-O Ito, Fujihashi K, Kido H.
    • Related Report
      2010 Final Research Report
  • [Presentation] 熱ストレスによる腸管上皮細胞間タイトジャンクションの崩壊機構2010

    • Author(s)
      矢野仁康、木戸博
    • Organizer
      第33回日本分子生物学会年会、第83回日本生化学会大会、合同学会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-07
    • Related Report
      2010 Final Research Report
  • [Presentation] Influenza-Cytokine-Protease Cycle in the pathogenesis of vascular hyperpermeability in severe influenza and its possible treatments.2010

    • Author(s)
      H Kido, J Chida, S Wang, H-Y Pan, M Yao.
    • Organizer
      第33回日本分子生物学会年会、第83回日本生化学会大会、合同学会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-07
    • Related Report
      2010 Final Research Report
  • [Presentation] 熱ストレによる腸管上皮細胞間タイトジャンクションの崩壊機構2010

    • Author(s)
      矢野仁康
    • Organizer
      第83回 日本生化学会大会
    • Place of Presentation
      神戸ポートアイランド(神戸市)
    • Year and Date
      2010-12-07
    • Related Report
      2010 Annual Research Report
  • [Presentation] Role of the host cellular processing proteases in influenza virus infection.2009

    • Author(s)
      Yuushi Okumura、Hiroshi Kido
    • Organizer
      International Proteolysis Society
    • Place of Presentation
      Gold Coast, Australia
    • Year and Date
      2009-10-27
    • Related Report
      2009 Annual Research Report
  • [Presentation] イブプロフェンは、Hsp70の発現量を低下させる事で、肺腺癌細胞に対するシスプラチンの抗腫瘍活性を増強する2009

    • Author(s)
      矢野仁康、木戸博
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸
    • Year and Date
      2009-10-24
    • Related Report
      2010 Final Research Report
  • [Presentation] インフルエンザ感染重症化の分子基盤と粘膜局所での感染予防の最前線2009

    • Author(s)
      木戸博、王司嘩、千田淳司、水野大、武井恒知
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸
    • Year and Date
      2009-10-23
    • Related Report
      2010 Final Research Report
  • [Presentation] Ibuprofen Increases Cisplatin-induced Apoptosis in Lung Adenocarcinoma by Suppressing Hsp70.2008

    • Author(s)
      M Yano, H Endo, H Kido
    • Organizer
      第31回日本分子生物学会年会、第81回日本生化学会大会、合同学会
    • Place of Presentation
      神戸
    • Year and Date
      2008-12-12
    • Related Report
      2010 Final Research Report
  • [Presentation] Influenzavirus-Cytokine-Protease Cycle in the Progression of Influenza-associated Encephalopathy2008

    • Author(s)
      Wang S
    • Organizer
      第81回日本生化学会
    • Place of Presentation
      神戸
    • Year and Date
      2008-12-10
    • Related Report
      2008 Annual Research Report
  • [Presentation] インフルエンザウイルス感染時におけるマウス各組織のATPレベル低下の機序の解明2008

    • Author(s)
      大西侑士
    • Organizer
      第81回日本生化学会
    • Place of Presentation
      神戸
    • Year and Date
      2008-12-10
    • Related Report
      2008 Annual Research Report
  • [Presentation] 解熱鎮痛剤ジクロフェナクのインフルエンザウイルス感染における効果2008

    • Author(s)
      山田博司
    • Organizer
      第56回日本ウイルス学会
    • Place of Presentation
      岡山
    • Year and Date
      2008-10-27
    • Related Report
      2008 Annual Research Report
  • [Presentation] インフルエンザ感染による多臓器不全の発症原因、“ウイルスーサイトカインープロテアーゼ"サイクル仮説のヒト血管内皮細胞を用いた証明の試み2008

    • Author(s)
      Wang S
    • Organizer
      第13回病態と治療におけるプロテアーゼとインヒビター学会
    • Place of Presentation
      大阪
    • Year and Date
      2008-08-22
    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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