Determining molecular mechanisms of statin regulatoryeffects on host and viral responses in the infections

• Project/Area Number: 21390306
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Infectious disease medicine
• Research Institution: Kitasato University
• Principal Investigator: TAKAHASHI Takashi 北里大学, 大学院・感染制御科学府, 教授 (00292855)
• Co-Investigator(Kenkyū-buntansha): ISHIGAKI Yasuhito 金沢医科大学, 付置研究所, 准教授 (20232275) ; MURAYAMA Tsugiya 北陸大学, 薬学部, 教授 (60159184) ; TAKANO Fumihide 金沢大学, 薬学系, 准教授 (20236251)
• Project Period (FY): 2009 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥15,470,000 (Direct Cost: ¥11,900,000、Indirect Cost: ¥3,570,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2011: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2010: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2009: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
• Keywords: ウイルス / 感染症 / 脂質 / 免疫学 / 遺伝子

Research Abstract

We determined host or viral molecules (transcripts, microRNAs,and translates) contributing to statin (mevastatin, lovastatin, simvastatin, or pravastatin)-induced regulatory effects on host responses and viral replications using in vitro infections with human cytomegalovirus or influenza virus. Association of apolipoprotein E genotypes with influenza susceptibility was also examined with benefit of statin-intervention before infection using clinical and animal investigations.

Research Products

• [Journal Article] Anticholesteremic agents, statins, modulate monocyte activation in cultured human THP-1 cells. (2013)
  • Author(s): Fumihide Takano, Takashi Takahashi, et al. (Fumihide Takano)
  • Journal Title: Oyo Yakuri Volume: 印刷中
  • NAID: 10031182020
  • Peer Reviewed
• [Journal Article] Anti-cytomegalovirus effects of tricin are dependent on CXCL11 (2012)
  • Author(s): Murayama T, Li Y, Takahashi T, Yamada R, Matsubara K, Tsuchida Y, Zheng X, Sadanari H.
  • Journal Title: Microbes Infect Volume: 14 Issue: 12 Pages: 1086-1092
  • DOI: 10.1016/j.micinf.2012.05.017
  • Peer Reviewed
• [Journal Article] Respiratory distress in human metapneumovirus infection with high inflammatory cytokinemia (2012)
  • Author(s): Takei T, Morozumi M, Kadota K, Miyamae T, Yokota S, Ubukata K, Iwata S, Takahashi T
  • Journal Title: J Exp Clin Med Volume: 4 Issue: 3 Pages: 189-193
  • DOI: 10.1016/j.jecm.2012.04.012
  • Peer Reviewed
• [Journal Article] Infectious diseases after the 2011 Great East Japan Earthquake (2012)
  • Author(s): Takahashi T, Goto M, Yoshida H, Sumino H, Matsui H
  • Journal Title: J Exp Clin Med Volume: 4 Issue: 1 Pages: 20-23
  • DOI: 10.1016/j.jecm.2011.11.013
  • Peer Reviewed
• [Journal Article] Respiratory distress in human metapneumovirus infection with high inflammatory cytokinemia (2012)
  • Author(s): Tomoaki Takei, Takashi Takahashi, et al
  • Journal Title: J Exp Clin Med Volume: VOL.4(印刷中)
  • Peer Reviewed
• [Journal Article] Characteristic findings of pediatric inpatients with pandemic (H1N1) 2009 virus infection among severe and nonsevere illnesses (2011)
  • Author(s): Okada T, Morozumi M, Matsubara K, Komiyama O, Ubukata K, Takahashi T, Iwata S
  • Journal Title: J Infect Chemother Volume: 17 Issue: 2 Pages: 238-245
  • DOI: 10.1007/s10156-010-0115-z
  • NAID: 10028171542
  • Peer Reviewed
• [Journal Article] Inhibitory effects of statins on cytomegalovirus production in human cells: comprehensive analysis of gene expression profiles (2011)
  • Author(s): Murayama T, Bi C, Li Y, Ishigaki Y, Takano F, Takegami T, Ohta T, Sumino H, Ubukata K, Takahashi T
  • Journal Title: J Exp Clin Med Volume: 3 Issue: 2 Pages: 40-45
  • DOI: 10.1016/j.jecm.2010.10.007
  • Peer Reviewed
• [Journal Article] Pandemic (H1N1) 2009-associated pneumonia in children, Japan (2011)
  • Author(s): Hasegawa M, Okada T, Sakata H, Nakayama E, Fuchigami T, Inamo Y, Mugishima H, Tajima T, Iwata S, Morozumi M, Ubukata K,Watanabe H, Takahashi T
  • Journal Title: Emerg Infect Dis Volume: 17 Issue: 2 Pages: 277-280
  • DOI: 10.3201/eid1702.091904
  • Peer Reviewed
• [Journal Article] インフルエンザの予防と治療 (2011)
  • Author(s): 高橋 孝
  • Journal Title: CARLISLE Volume: 16 Pages: 1-3
  • URL: http://www.yoshida-pharm.com/carlisle/1601/outline.html
• [Journal Article] Inhibitory effects of statins on cytomegalovirus production in human cells : comprehensive analysis of gene expression profiles. (2011)
  • Author(s): Tsugiya Murayama, Yasuhito Ishigaki, Takashi Takahashi, et al.
  • Journal Title: J Exp Clin Med Volume: VOL.3 Pages: 40-45
  • Peer Reviewed
• [Journal Article] Pandemic (H1N1) 2009-associated pneumonia in children, Japan. (2011)
  • Author(s): Maki Hasegawa, Takashi Takahashi, et al.
  • Journal Title: Emerg Infect Dis Volume: VOL.17 Pages: 277-280
  • Peer Reviewed
• [Journal Article] インフルエンザの予防と治療 (2011)
  • Author(s): 高橋孝
  • Journal Title: CARLISLE Volume: VOL.16 Pages: 1-3
• [Journal Article] Bronchial casts and pandemic (H1N1) 2009 virus infection (2010)
  • Author(s): Hasegawa M, Inamo Y, Fuchigami T, Hashimoto K, Morozumi M, Ubukata K, Watanabe H, Takahashi T
  • Journal Title: Emerg Infect Dis Volume: 16 Issue: 2 Pages: 344-346
  • DOI: 10.3201/eid1602.091607
  • Peer Reviewed
• [Journal Article] Spontaneous pneumomediastinum complicating pneumonia in children infected with the 2009 pandemic influenza A (H1N1) virus (2010)
  • Author(s): Hasegawa M, Hashimoto K, Morozumi M, Ubukata K, Takahashi T, Inamo Y
  • Journal Title: Clin Microbiol Infect Volume: 16 Issue: 2 Pages: 195-199
  • DOI: 10.1111/j.1469-0691.2009.03086.x
  • Peer Reviewed
• [Journal Article] Bronchial casts and pandemic(H1N1)2009 virus infection. (2010)
  • Author(s): Maki Hasegawa, Kimiko Ubukata, Takashi Takahashi, et al.
  • Journal Title: Emerg Infect Dis VOL.16 Pages: 344-346
  • Peer Reviewed
• [Journal Article] Spontaneous pneumomediastinum complicating pneumonia in children infected with the 2009 pandemic influenza A(H1N1)virus. (2010)
  • Author(s): Maki Hasegawa, Kimiko Ubukata, Takashi Takahashi, et al.
  • Journal Title: Clin Microbiol Infect VOL.16 Pages: 195-199
  • Peer Reviewed
• [Journal Article] Anticholesteremic agents, statins, modulate monocyte activation in cultured human THP-1 cells
  • Author(s): Takano F, Bi C, Ishigaki Y, Yoshida H, Sakurada C, Takahashi T
  • Journal Title: Oyo Yakuri Volume: (印刷中)
  • NAID: 10031182020
  • Peer Reviewed
• [Presentation] インフルエンザウイルスに対するスタチン系薬の抗ウイルス効果 (2013)
  • Author(s): 高橋 孝
  • Organizer: 第24回日本臨床微生物学会総会
  • Place of Presentation: 横浜, 神奈川
  • Year and Date: 2013-02-02
• [Presentation] インフルエンザウイルスに対するスタチン系薬の抗ウイルス効果 (2013)
  • Author(s): 高橋 孝、他．(高橋 孝)
  • Organizer: 第24回日本臨床微生物学会総会
  • Place of Presentation: パシフィコ横浜 (神奈川県)
• [Presentation] Inhibitory effects of simvastatin on human cytomegalovirus replication through altered expression of a chemokine, C-X-C motif ligand 11 in human embryonic lung cells (2012)
  • Author(s): Takahashi T
  • Organizer: 11th East Asian Conference on Infection Control and Prevention
  • Place of Presentation: Tokyo, Japan.
  • Year and Date: 2012-11-15
• [Presentation] Infectious diseases after the 2011 earthquake off the Pacific Coast of Tohoku (2012)
  • Author(s): Takahashi T
  • Organizer: 12thJoint Symposium of Robert Koch Institute and the Kitasato Institute
  • Place of Presentation: Berlin, Germany
  • Year and Date: 2012-10-09
• [Presentation] Inhibitory effects of simvastatin on human cytomegalovirus replication through altered expression of a chemokine, C-X-C motif ligand 11 in human embryonic lung cells. (2012)
  • Author(s): Takashi Takahashi, Tsugiya Murayama, et al. (Takashi Takahashi)
  • Organizer: 11th East Asian Conference on Infection Control and Prevention
  • Place of Presentation: Tokyo, Japan
• [Presentation] Infectious diseases after the 2011 earthquake off the Pacific Coast of Tohoku. (2012)
  • Author(s): Takashi Takahashi. (Takashi Takahashi)
  • Organizer: 12th Joint Symposium of Robert Koch Institute and the Kitasato Institute
  • Place of Presentation: Berlin, Germany
  • Invited
• [Presentation] Inhibitory effect of statins on expression of the major immediate-early gene of human cytomegalovirus (HCMV) in HCMV-infected cells (2011)
  • Author(s): Sadanari H, (Murayama T)
  • Organizer: International Union of Microbiological Societies 2011 congress
  • Place of Presentation: Sapporo, Japan
  • Year and Date: 2011-09-15
• [Presentation] スタチン系薬によるヒトサイトメガロウイルスの複製抑制と感染細胞遺伝子発現の網羅的解析 (2011)
  • Author(s): 高橋 孝
  • Organizer: 第85回日本感染症学会総会
  • Place of Presentation: 港区, 東京
  • Year and Date: 2011-04-22
• [Presentation] Tricin、4', 5, 7-trihydroxy-3', 5'-dimethoxyflavoneによる抗ヒトサイトメガロウイルス効果の機序について (2011)
  • Author(s): 李 瑩, (村山次哉)
  • Organizer: 日本薬学会第131 年会
  • Place of Presentation: 静岡市, 静岡
  • Year and Date: 2011-03-28
• [Presentation] Inhibitory effects of various statins on cytomegalovirus replication in human cells (2010)
  • Author(s): Takahashi T
  • Organizer: 50th Annual Meeting of Interscience Conference of AAC
  • Place of Presentation: Boston, USA
  • Year and Date: 2010-09-13
• [Presentation] Inhibitory effects of various statins on cytomegalovirus replication in human cells. (2010)
  • Author(s): Takashi Takahashi, Tsugiya Murayama, Yasuhito Ishigaki, et al.
  • Organizer: 50^<th> Annual Meeting of ICAAC
  • Place of Presentation: Boston, USA
  • Year and Date: 2010-09-13
• [Presentation] スタチン系薬剤による抗ヒトサイトメガロウイルス作用の検討 (2010)
  • Author(s): 瑩, (村山次哉)
  • Organizer: 日本薬学会第130 年会
  • Place of Presentation: 岡山, 岡山
  • Year and Date: 2010-03-28
• [Presentation] スタチン系薬剤による抗ウイルス効果の検討 (2009)
  • Author(s): 李 瑩, (村山次哉)
  • Organizer: 第57回日本ウイルス学会学術集会
  • Place of Presentation: 千代田区, 東京
  • Year and Date: 2009-10-25
• [Presentation] スタチン系薬剤による抗ウイルス効果の検討 (2009)
  • Author(s): 李瑩、高橋孝、村山次哉, 他
  • Organizer: 第57回日本ウイルス学会学術集会
  • Place of Presentation: 都市センターホテル(東京都)
  • Year and Date: 2009-10-25
• [Presentation] スタチン系薬剤のヒトサイトメガロウイルスに対する増殖抑制効果 (2009)
  • Author(s): 畢 長暁, (村山次哉)
  • Organizer: 日本薬学会北陸支部第120回例会
  • Place of Presentation: 金沢, 石川
  • Year and Date: 2009-07-11
• [Book] ヒトメタニューモウイルス新興呼吸器感染症「呼吸器疾患最新の治療 2010-2012」 (2010)
  • Author(s): 高橋 孝(監修:貫和敏博, 杉山幸比古, 門田淳一).
  • Publisher: 南江堂
• [Book] インフルエンザ・ノロウイルス感染症「新老年学第3版」 (2010)
  • Author(s): 高橋 孝(監修:大内尉義, 秋山弘子)
  • Publisher: 東京大学出版会
• [Remarks]
  • URL: http://www.kitasato-u.ac.jp/lisci/life/chart/LSI-lab15.html
• [Remarks] 北里大学大学院感染制御科学府・感染症学研究室・研究の概要および研究業績
  • URL: http://www.kitasato-u.ac.jp/lisci/life/chart/LSI-lab15.html