Relation of the cytotoxic effect of Mycobacterium tuberculosis on host cells and the signal transduction from interlukin 1 (IL-1) receptor and IL-1R related receptors

• Project/Area Number: 19590122
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Environmental pharmacy
• Research Institution: Nagoya City University
• Principal Investigator: TAKII Takemasa Nagoya City University, 大学院・薬学研究科, 准教授 (80244573)
• Co-Investigator(Kenkyū-buntansha): 小野嵜 菊夫 名古屋市立大学, 大学院・薬学研究科, 教授 (20101313)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2007: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 微生物 / 感染症学 / 結核菌 / ワクチン / サイトカイン / 病原性

Research Abstract

Mycobacterium species possess lipid rich cell wall, which is well known to induce innate immune response in host cells through toll like receptors(TLRs). The signal transduction form the receptor is partly shared with it form interleukin 1 receptor (IL-1R). We compared the inducing activity of NF-kB between M. tuberculosis and its vaccine strain BCG. The activity related to their virulence.

Research Products

• [Journal Article] IL-1-induced ERK1/2 activation up-regulates p21(Waf1/Cip1) protein by inhibition of degradation via ubiquitin-independent pathway in human melanoma cells A375. (2010)
  • Author(s): Arakawa T, Hayashi H, Itoh S, Takii T, Onozaki K.
  • Journal Title: Biochem Biophys Res Commun. 392(3) Pages: 369-72
• [Journal Article] Staphylococcal superantigen-like protein 10 (SSL10) binds to human immunoglobulin G (IgG) and inhibits complement activation via the classical pathway. (2010)
  • Author(s): Itoh S, Hamada E, Kamoshida G, Yokoyama R, Takii T, Onozaki K, Tsuji T.
  • Journal Title: Mol Immunol. 47(4) Pages: 932-8
• [Journal Article] Synthesis of new sugar derivatives and evaluation of their antibacterial activities against Mycobacterium tuberculosis. (2009)
  • Author(s): Horita Y, Takii T, Chiba T, Kuroishi R, Maeda Y, Kurono Y, Inagaki E, Nishimura K, Yamamoto Y, Abe C, Mori M, Onozaki K.
  • Journal Title: Bioorg Med Chem Lett. 19(22) Pages: 6313-6
• [Journal Article] Comparable studies of immunostimulating activities in vitro among Mycobacterium bovis bacillus Calmette-Guerin (BCG) substrains. (2009)
  • Author(s): Hayashi D, Takii T, Fujiwara N, Fujita Y, Yano I, Yamamoto S, Kondo M, Yasuda E, Inagaki E, Kanai K, Fujiwara A, Kawarazaki A, Chiba T, Onozaki K.
  • Journal Title: FEMS Immunol Med Microbiol. 56(2) Pages: 116-28
• [Journal Article] Separation and molecular characterization of mycolic acid from the cell wall skeleton of Mycobacterium bovis BCG Tokyo 172 (SMP-105) and BCG substrains by normal-phase high performance liquid chromatography and liquid chromatography/mass spectrometry. (2009)
  • Author(s): Uenishi Y, Takii T, Yano I, Sunagawa M.
  • Journal Title: J Microbiol Methods. 77(3) Pages: 320-2
• [Journal Article] Synthesis of new sugar derivatives and evaluation of their antibacterial activities against Mycobacterium tuberculosis (2009)
  • Author(s): Horita Y, Takii T, Chiba T, Kuroishi R, Maeda Y, Kurono Y, Inagaki E, Nishimura K, Yamamoto Y, Abe C, Mori M, Onozaki K.
  • Journal Title: Bioorg Med Chem Lett. 19(22) Pages: 6313-6316
  • Peer Reviewed
• [Journal Article] Comparable studies of immunostimulating activities in vitro among Mycobacterium bovis bacillus Calmette-Guerin(BCG)substrains (2009)
  • Author(s): Hayashi D, Takii T, Fujiwara N, Fujita Y, Yano I, Yamamoto S, Kondo M, Yasuda E, Inagaki E, Kanai K, Fujiwara A, Kawarazaki A, Chiba T, Onozaki K.
  • Journal Title: FEMS Immunol Med Microbiol. 56(2) Pages: 116-128
  • Peer Reviewed
• [Journal Article] Separation and molecular characterization of mycolic acid from the cell wall skeleton of Mycobacterium bovis BCG Tokyo 172(SMP-105)and BCG substrains by normal-phase high performance liquid chromatography and liquid chromatography/mass spectrometry (2009)
  • Author(s): Uenishi Y, Takii T, Yano I, Sunagawa M.
  • Journal Title: J Microbiol Methods. 77(3) Pages: 320-322
  • Peer Reviewed
• [Journal Article] Cigarette smoke condensate upregulates the gene and protein expression of proinflammatory cytokines in human fibroblast-like synoviocyte line. (2008)
  • Author(s): Shizu M, Itoh Y, Sunahara R, Chujo S, Hayashi H, Ide Y, Takii T, Koshiko M, Chung SW, Hayakawa K, Miyazawa K, Hirose K, Onozaki K.
  • Journal Title: J Interferon Cytokine Res. 28(8) Pages: 509-21
• [Journal Article] The interaction with Sp1 and reduction in the activity of histone deacetylase 1 are critical for the constitutive gene expression of IL-1 alpha in human melanoma cells. (2008)
  • Author(s): Enya K, Hayashi H, Takii T, Ohoka N, Kanata S, Okamoto T, Onozaki K.
  • Journal Title: J Leukoc Biol. 83(1) Pages: 190-9
• [Journal Article] The interaction with Spl and reduction in the activity of histone deacetylase 1 are critical for the constitutive gene expression of IL-1 alpha in human melanoma cells (2008)
  • Author(s): Enya K, Hayashi H, Takii T, Ohoka N, Kanata S, Okamoto T, Onozaki K.
  • Journal Title: Journal of Leukocyte Biology 83・1 Pages: 190-199
  • Peer Reviewed
• [Journal Article] Cigarette smoke condensate upregulates the gene and protein expression of proinflammatory cytokines in human fibroblast-like synoviocyte line. (2008)
  • Author(s): Shizu M, Itoh Y, Sunahara R, Chujo S, Hayashi H, Ide Y, Takii T, Koshiko M, Chung SW, Hayakawa K, Miyazawa K, Hirose K. Onozaki K
  • Journal Title: Journal of Interferon Cytokine Research 28・8 Pages: 509-521
  • Peer Reviewed
• [Journal Article] The interaction with Spl and reduction in the activity of histone deacetylase 1 are critical for the constitutive gene expression of IL-1 alpha in human melanoma cells. (2008)
  • Author(s): Enya K, Hayashi H, Takii T, Ohoka N, Kanata S, Okamoto T, Onozaki K.
  • Journal Title: J. Leukoc. Biol. 83・1 Pages: 190-199
  • Peer Reviewed
• [Journal Article] Dihydrotestosterone inhibits tumor necrosis factor alpha induced interleukin-1alpha mRNA expression in rheumatoid fibroblast-like synovial cells. (2007)
  • Author(s): Itoh Y, Hayashi H, Xu J, Takii T, Miyazawa K, Ariga H, Akahoshi T, Waguri-Nagaya Y, Otsuka T, Okamoto T, Onozaki K.
  • Journal Title: Biol Pharm Bull. 30(6) Pages: 1140-3
  • NAID: 120005350115
• [Journal Article] Synthesis of new sugar derivatives from Stachys sieboldi Miq and antibacterial evaluation against Mycobacterium tuberculosis, Mycobacterium avium, and Staphylococcus aureus. (2007)
  • Author(s): Chiba T, Takii T, Nishimura K, Yamamoto Y, Morikawa H, Abe C, Onozaki K.
  • Journal Title: Bioorg Med Chem Lett. 17(9) Pages: 2487-91
• [Journal Article] Synthesis of new sugar derivatives from Stachys sieboldi Miq and antibacterial evaluation against Mycobacterium tuberculosis, Mycobacterium avium, and Staphylococcus aureus. (2007)
  • Author(s): Chiba T, Takii T, Nishimura K, Yamamoto Y, Morikawa H, Abe C, Onozaki K.
  • Journal Title: Bioorg Med Chem Lett. 17・9 Pages: 2487-2791
  • Peer Reviewed
• [Journal Article] Dihydrotestosterone inhibits tumor necrosis factor alpha induced interleukin-lalphamRNA expression in rheumatoid fibroblast-like synovial cells. (2007)
  • Author(s): Itoh Y, Hayashi H, Xu J, Takii T, Miyazawa K, Ariga H, Akahoshi T, Waguri-Nagaya Y, Otsuka T, Okamoto T, Onozaki K.
  • Journal Title: Biol. Pharm. Bull. 30・6 Pages: 1140-1143
  • Peer Reviewed
• [Presentation] 黄色ブドウ球菌のスーパー抗原様タンパク質SSL10はヒトIgGに結合し古典経路による補体活性化を抑制する (2010)
  • Author(s): 伊藤佐生智, 濱田恵里, 鴨志田剛, 横山領介, 瀧井猛将, 小野嵜菊夫, 辻勉
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-30
• [Presentation] Mycobacterium bovis BCGの宿主細胞内生存能と抗原性の発現に関する研究 (2010)
  • Author(s): 谷口恵一, 瀧井猛将, 安田恵実, 林大介, 向井徹, 山本三郎, 小野嵜菊夫
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-30
• [Presentation] 男性ホルモンによる関節リウマチ滑膜細胞からの炎症性サイトカインの産生抑制 (2010)
  • Author(s): 許鍵, 伊藤友香, 瀧井猛将, 林秀敏, 小野嵜菊夫
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-30
• [Presentation] タバコと関節リウマチに関する研究 (2010)
  • Author(s): 岡本翔佑, 中條里美, 瀧井猛将, 林秀敏, 早川和一, 小野嵜菊夫
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-30
• [Presentation] インターロイキン-1によるヒトメラノーマ細胞増殖抑制機構の解析 (2010)
  • Author(s): 荒川友博, 林秀敏, 伊藤佐生智, 瀧井猛将, 小野嵜菊夫
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-28
• [Presentation] 抗酒薬ジスルフィラムの抗結核作用についての検討 (2010)
  • Author(s): 堀田康弘, 瀧井猛将, 小川賢二, 稲垣衣美, 小野嵜菊夫
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-28
• [Presentation] OCT313の誘導体の作製と抗結核作用の解析 (2010)
  • Author(s): 黒石隆司, ほか
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-28
• [Presentation] トリ型結核菌亜種のアンモニア産生におけるArginine deiminaseの関与 (2010)
  • Author(s): 山本龍二, 瀧井猛将, 堀田康弘, 小川賢二, 小野嵜菊夫
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-28
• [Presentation] 喫煙と関節リウマチ:たばこの煙抽出物は滑膜細胞から炎症性サイトカインの産生を誘導し、コラーゲン誘導性関節炎の発症を増強する (2009)
  • Author(s): 岡本翔佑, 林秀敏, 瀧井猛将, 小野嵜菊夫
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-04
• [Presentation] 黄色ブドウ球菌スーパー抗原様タンパク質SSL5はMMP-9の活性を抑制し, 好中球の浸潤を阻害する (2009)
  • Author(s): 伊藤佐生智, 横山領介, 辻勉, 瀧井猛将, 小野崎菊夫
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-04-12
• [Book] 化学療法学-病原微生物・がんと戦う- (2009)
  • Author(s): 上野芳夫, 大村智, 田中晴雄, 土屋友房
  • Publisher: 南江堂
• [Book] 化学療法学 病原微生物・がんと戦う (2009)
  • Author(s): 田中康夫, 他
  • Total Pages: 315
  • Publisher: 南江堂
• [Remarks]
  • URL: http://www.phar.nagoya-cu.ac.jp/hp/esk/index.html
• [Remarks]
  • URL: http://www.phar.nagoya-cu.ac.jp/hp/esk/index.html
• [Patent(Industrial Property Rights)] 抗結核薬及びその用途 (2009)
  • Inventor(s): 瀧井猛将, 堀田康弘, 稲垣衣美, 小野嵜菊夫
  • Industrial Property Rights Holder: 名古屋市立大学
  • Industrial Property Number: 2009-021026
  • Filing Date: 2009-01-31
• [Patent(Industrial Property Rights)] 抗結核化合物及びその用途 (2009)
  • Inventor(s): 瀧井猛将, 堀田康弘, 稲垣衣美, 小野嵜菊夫
  • Industrial Property Rights Holder: 名古屋市立大学
  • Industrial Property Number: 2009-021026
  • Filing Date: 2009-01-31
• [Patent(Industrial Property Rights)] 抗結核化合物、及びその利用 (2009)
  • Inventor(s): 瀧井猛将, 堀田康弘, 小野寄菊夫, 千葉拓, 森雅美
  • Industrial Property Rights Holder: 名古屋市立大学
  • Industrial Property Number: 2009-037185
  • Filing Date: 2009-02-19
• [Patent(Industrial Property Rights)] 抗結核化合物及びその利用 (2008)
  • Inventor(s): 瀧井猛将, 堀田康弘, 小野嵜菊夫, 千葉拓, 森雅美
  • Industrial Property Rights Holder: 名古屋市立大学
  • Industrial Property Number: 2008-059903
  • Filing Date: 2008-03-10