Analysis of Severe Influenza Pneumonia -Control of Host and Pathogen Factors in Influenza and Bacteria Co-infected Mice Models

• Project/Area Number: 21790774
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Respiratory organ internal medicine
• Research Institution: Nagasaki University
• Principal Investigator: SEKI Masafumi Nagasaki University, 大学院・医歯薬学総合研究科, 助教 (80432970)
• Co-Investigator(Kenkyū-buntansha): KOHNO Shigeru 長崎大学, 大学院・医歯薬学総合研究科, 助教 (80136647)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: インフルエンザ / 細菌感染 / 肺炎 / 新規抗インフルエンザ薬 / ペラミビル

Research Abstract

We examined the mechanisms of severe influenza virus-related pneumonia. In pathogens factor, quorum sensing related genes were deleted in Pseudomonas, and we infected them to mice. Toxin were decreased, but no significant differences were found in vivo. However, apoptosis were detected in virus and Streptococcus co-infected mice, and excessive inflammation and pulmonary edema according to cytokine storm were observed in TLR-related genes-deleted mice by influenza virus infection alone. Excessive inflammation might be related to progression of severe pneumonia

Research Products

• [Journal Article] Critical role of IRAK-M in regulating chemokine-dependent deleterious inflammation in murine influenza pneumonia. (2010)
  • Author(s): Seki M, Kohno S, Newstead M, Zeng X, Bhan U, Lukacs N, Kunkel S, Standiford T.
  • Journal Title: J Immunol. 184 Pages: 1410-1418
• [Journal Article] A case of intravascular large B-cell lymphoma(IVLBCL)with no abnormal findings on chest computed tomography diagnosed by random transbronchial lung biopsy. (2010)
  • Author(s): Kaku N, Seki M, Doi S, Hayashi T, Imanishi D, Imamura Y, Kurihara S, Miyazaki T, Izumikawa K, Kakeya H, Yamamoto Y, Yanagihara K, Tashiro T, Kohno S.
  • Journal Title: Intern Med. 49 Pages: 2697-2701
  • NAID: 130000413430
• [Journal Article] for the S-021812 Clinical Study Group.Efficacy and safety of intravenous peramivir for the treatment of seasonal influenza. (2010)
  • Author(s): Kohno S, Kida H, Mizuguchi M, Shimada J
  • Journal Title: Antimicrob Agents Chemother 54 Pages: 4568-4574
• [Journal Article] Legionella pneumophila Induces Cathepsin B-dependent Necrotic Cell Death with Releasing High Mobility Group Box1 in Macrophages. (2010)
  • Author(s): Morinaga Y, Yanagihara K, Nakamura S, Hasegawa H, Seki M, Izumikawa K, Kakeya H, Yamamoto Y, Yamada Y, Kohno S, Kamihira S.
  • Journal Title: Respir Res. 22;11 Pages: 158-158
• [Journal Article] Importance of Controlling Drug-resistant Pseudomonas aeruginosa Infection: Experience from Lung Transplantation in a Cystic Fibrosis Case. (2010)
  • Author(s): Yamamoto Y, Izumikawa K, Hara A, Fujita H, Amenomori M, Sakamoto N, Seki M, Kakeya H, Yanagihara K, Takasaki K, Miyazaki T, Tsuchiya T, Yamasaki N, Tagawa T, Nagayasu T, Kohno S.
  • Journal Title: Intern Med. 49 Pages: 2353-2358
  • NAID: 130000413356
• [Journal Article] In vivo efficacy of sivelestat in combination with pazufloxacin against Legionella pneumonia. (2010)
  • Author(s): Morinaga Y, Yanagihara K, Araki N, Yamada K, Seki M, Izumikawa K, Kakeya H, Yamamoto Y, Yamada Y, Kohno S, Kamihira S.
  • Journal Title: Exp Lung Res. 36 Pages: 484-490
  • NAID: 120006984903
• [Journal Article] Evaluation of pathogen detection from clinical samples by real-time polymerase chain reaction using a sepsis pathogen DNA detection kit. (2010)
  • Author(s): Yanagihara K, Kitagawa Y, Tomonaga M, Tsukasaki K, Kohno S, Seki M, Sugimoto H, Shimazu T, Tasaki O, Matsushima A, Ikeda Y, Okamoto S, Aikawa N, Hori S, Obara H, Ishizaka A, Hasegawa N, Takeda J, Kamihira S, Sugahara K, Asari S, Murata M, Kobayashi Y, Ginba H, Sumiyama Y, Kitajima M.
  • Journal Title: Crit Care. 14
• [Journal Article] Roles of calcineurin and Crz1 in antifungal susceptibility and virulence of Candida glabrata. (2010)
  • Author(s): Miyazaki T, Yamauchi S, Inamine T, Nagayoshi Y, Saijo T, Izumikawa K, Seki M, Kakeya H, Yamamoto Y, Yanagihara K, Miyazaki Y, Kohno S.
  • Journal Title: Antimicrob Agents Chemother. 54 Pages: 1639-1643
  • NAID: 120006984565
• [Journal Article] Diffuse Alveolar Hemorrhage following Itraconazole Injection. (2010)
  • Author(s): Izumikawa K, Nakano K, Kurihara S, Imamura Y, Yamamoto K, Miyazaki T, Sakamoto N, Seki M, Ishimatsu Y, Kakeya H, Yamamoto Y, Yanagihara K, Tsuchiya T, Yamasaki N, Tagawa T, Mukae H, Nagayasu T, Kohno S.
  • Journal Title: Intern Med. 49 Pages: 497-500
  • NAID: 130000251704
• [Journal Article] Role of the Slt2 mitogen-activated protein kinase pathway in cell wall integrity and virulence in Candida glabrata. (2010)
  • Author(s): Miyazaki T, Inamine T, Yamauchi S, Nagayoshi Y, Saijo T, Izumikawa K, Seki M, Kakeya H, Yamamoto Y, Yanagihara K, Miyazaki Y, Kohno S.
  • Journal Title: FEMS Yeast Res. 10 Pages: 343-352
  • NAID: 120006984540
• [Journal Article] Skn7p Is Involved in Oxidative Stress Response and Virulence of Candida glabrata. (2010)
  • Author(s): Saijo T, Miyazaki T, Izumikawa K, Mihara T, Takazono T, Kosai K, Imamura Y, Seki M, Kakeya H, Yamamoto Y, Yanagihara K, Kohno S.
  • Journal Title: Mycopathologia. 169 Pages: 81-90
• [Journal Article] Efficacy of clarithromycin against experimentally induced pneumonia caused by clarithromycin-resistant Haemophilus influenzae in mice. (2010)
  • Author(s): Nakamura S, Yanagihara K, Araki N, Yamada K, Morinaga Y, Izumikawa K, Seki M, Kakeya H, Yamamoto Y, Kamihira S, Kohno S.
  • Journal Title: Antimicrob Agents Chemother. 54 Pages: 757-762
  • NAID: 120006984671
• [Journal Article] 平成21年度北里柴三郎記念学術奨励賞受賞記念論文インフルエンザ関連肺炎の重症化機序の解析と治療法の検討 (2010)
  • Author(s): 関雅文、田中章貴、小佐井康介、河野茂
  • Journal Title: 日本感染症学会雑誌 84 Pages: 689-693
• [Journal Article] 私達の研究インフルエンザウイルス肺炎と細菌感染の合併による重症化機序 (2010)
  • Author(s): 関雅文、小佐井康介、田中章貴、河野茂
  • Journal Title: 化学療法の領域 26 Pages: 2460-2466
• [Journal Article] 話題のくすり ペラミビル水和物 (2010)
  • Author(s): 関雅文、河野茂
  • Journal Title: 日本病院薬剤師会雑誌 46 Pages: 1553-1555
• [Journal Article] 一日一回投与時代の抗菌化学療-新規抗インフルエンザ薬の新たな展開 (2010)
  • Author(s): 関雅文、河野茂
  • Journal Title: 化学療法の領域 26 Pages: 1425-1430
• [Journal Article] 新型インフルエンザの病態の特徴-季節性インフルエンザと比較して (2010)
  • Author(s): 関雅文、河野茂
  • Journal Title: 呼吸器科 17 Pages: 24-28
• [Journal Article] 新型インフルエンザの出現と対策 (2010)
  • Author(s): 河野茂、関雅文
  • Journal Title: 呼吸器科 17 Pages: 1-5
• [Journal Article] 新しい抗インフルエンザ薬 (2010)
  • Author(s): 関雅文、河野茂
  • Journal Title: 日内誌 11 Pages: 2735-2739
  • NAID: 10027509089
• [Journal Article] ペラミビル (2010)
  • Author(s): 河野茂、関雅文
  • Journal Title: インフルエンザ 11 Pages: 360-364
• [Journal Article] ペラミビル (2010)
  • Author(s): 河野茂、関雅文
  • Journal Title: 臨床と微生物 10 Pages: 549-552
• [Journal Article] 新規治療薬の展望1)抗インフルエンザ薬 (2010)
  • Author(s): 関雅文、河野茂
  • Journal Title: 感染と抗菌薬 13 Pages: 372-376
• [Journal Article] 新しい抗インフルエンザ薬 (2010)
  • Author(s): 田中章貴、関雅文、小佐井康介、河野茂
  • Journal Title: ペラミビル 臨床と研究 87 Pages: 1702-1706
  • NAID: 10027509089
• [Journal Article] Critical role of IRAK-M in regulating chemokine-dependent deleterious inflammation in murine influenza pneumonia. (2010)
  • Author(s): Seki M, Kohno S, Newstead M, Zeng X, Bhan U, Lukacs N, Kunkel S, Standiford T.
  • Journal Title: J Immunol Volume: 184 Pages: 1410-1418
  • Peer Reviewed
• [Journal Article] 新しい抗インフルエンザ薬 (2010)
  • Author(s): 関雅文、河野茂
  • Journal Title: 日本内科学会雑誌 Volume: 99 Pages: 2735-2739
  • NAID: 10027509089
• [Journal Article] 平成21年度北里柴三郎記念学術奨励賞受賞記念論文インフルエンザ関連肺炎の重症化機序の解析と治療法の検討 (2010)
  • Author(s): 関雅文、田中章貴、小佐井康介、河野茂
  • Journal Title: 日本感染症学会雑誌 Volume: 84 Pages: 689-693
• [Journal Article] Critical role of IRAK-M in regulating chemokine-dependent deleterious inflammation in murine influenza pneumonia. (2010)
  • Author(s): Seki M, Kohno S, Newstead M, et al.
  • Journal Title: J.Immunol. 184 Pages: 1410-1418
  • Peer Reviewed
• [Journal Article] Expression and analysis of Platelet activating factor (PAF) related molecule in severe pneumonia in mice due to influenza virus and bacterial co-infection using by DNA microarray (2009)
  • Author(s): Seki M, Kosai K, Hara A, et al.
  • Journal Title: Jpn J Infect Dis. 62 Pages: 6-10
  • Peer Reviewed
• [Journal Article] 院内肺炎ガイドライン2008 (2009)
  • Author(s): 関雅文、河野茂
  • Journal Title: 呼吸 28 Pages: 715-719
• [Presentation] Critical Role of IRAK-M in Regulating Chemokine-dependent Deleterious Inflammation in Murine Influenza Pneumonia (2010)
  • Author(s): 関雅文
  • Organizer: American Thoracic Society(米国胸部学会)
  • Place of Presentation: 米国:ニューオリンズ(口頭発表演題)
  • Year and Date: 2010-05-28
• [Presentation] ランチョンセミナー最新の抗インフルエンザ薬とガイドラインに沿った呼吸器感染症診療 (2010)
  • Author(s): 関雅文
  • Organizer: 第25回環境感染学会
  • Place of Presentation: 東京
• [Presentation] ミニシンポジウムノックアウトマウスを用いた重症インフルエンザ肺炎の発症機序の解析 (2010)
  • Author(s): 関雅文、小佐井康介、田中章貴、河野茂
  • Organizer: 第84回日本感染症学会総会
  • Place of Presentation: 京都
• [Presentation] English Mini Symposium Critical Role of IRAK-M in Regulating Chemokine-dependent Deleterious Inflammation in Murine Influenza Pneumonia (2010)
  • Author(s): Seki M, etal.
  • Organizer: 第50回日本呼吸器学会総会
  • Place of Presentation: 東京
• [Presentation] Mini Symposium (Oral presentation) Critical Role of IRAK-M in Regulating Chemokine-dependent Deleterious Inflammation in Murine Influenza Pneumonia (2010)
  • Author(s): Seki M, Kohno S, etal.
  • Organizer: ATS(米国胸部疾患学会)
  • Place of Presentation: ニューオーリンズ
• [Presentation] シンポジウムインフルエンザに合併する重症インフルエンザの発症機序の解析 (2010)
  • Author(s): 関雅文
  • Organizer: 第58回日本化学療法学会総会
  • Place of Presentation: 長崎
• [Presentation] 大分イブニングシンポジウム語ろう日本の新型インフルエンザ新しい抗インフルエンザ薬と今後のインフルエンザ診療 (2010)
  • Author(s): 関雅文
  • Organizer: 西日本化学療法学会
• [Presentation] Proteomic analysis and protease inhibitor therapy for influenza-related pneumonia (2009)
  • Author(s): Seki M, Tanaka A, Kosai K, et al.
  • Organizer: 国際化学療法学会(ISC)
  • Place of Presentation: トロント(カナダ)
  • Year and Date: 2009-06-19
• [Book] VI基礎疾患(糖尿病・喘息・COPD)を持つ患者への対応これでわかるインフルエンザ診療のポイント(藤田次郎編) (2010)
  • Author(s): 関雅文、河野茂
  • Publisher: 南江堂(東京)
• [Book] これでわかるインフルエンザ診療のポイントVI基礎疾患(糖尿病・喘息・COPD)を持つ患者への対応 (2010)
  • Author(s): 関雅文、河野茂
  • Total Pages: 7
  • Publisher: 南江堂(東京)
• [Remarks]
  • URL: http://www.med.nagasaki-u.ac.jp/intmed-2/index.html
• [Remarks]
  • URL: http://www.med.nagasaki-u.ac.jp/mmi/mcm/index.html
• [Remarks]
  • URL: http://www.med.nagasaki-u.ac.jp/intmed-2/index.html
• [Remarks]
  • URL: http://www.med.nagasaki-u.ac.jp/mmi/mcm/index.html