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

2010 Fiscal Year Final Research Report

• Project/Area Number: 20611013
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Chemical biology
• Research Institution: The University of Tokushima
• Principal Investigator: YANO Mihiro The University of Tokushima, 疾患酵素学研究センター, 准教授 (40304555)
• Co-Investigator(Kenkyū-buntansha): KIDO Hiroshi 徳島大学, 疾患酵素学研究センター, 教授 (50144978)
• Project Period (FY): 2008 – 2010
• 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

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.

Research Products

• [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
  • 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
  • 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
• [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
  • 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
  • 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) Pages: 1127-1137,778-783
  • 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
  • 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
  • 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
  • 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.
• [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
• [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
• [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
• [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
• [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