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2006 Fiscal Year Final Research Report Summary

Analysis of the cytotoxicity of virulent Mycobacterium tuberculosis to human fibroblast cells

Research Project

Project/Area Number 17590105
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental pharmacy
Research InstitutionDepartment of Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Nagoya City University

Principal Investigator

TAKII Takemasa  Graduate School of Pharmaceutical Sciences, Department of Molecular Health Sciences, Lecturer, 大学院薬学研究科, 講師 (80244573)

Co-Investigator(Kenkyū-buntansha) ONOZAKI Kikuo  Graduate School of Pharmaceutical Sciences, Department of Molecular Health Sciences, Professor, 大学院薬学研究科, 教授 (20101313)
Project Period (FY) 2005 – 2006
KeywordsMycobacterium tuberculosis / Pathogenesis, Virulence / Cytotoxicity / Cytokine / Interleukin / Drug resistance / Antibiotics / Vaccine
Research Abstract

We have previously reported that virulent Mycobacterium tuberculosis exhibits cytotoxicty to human embryonic lung fibroblast cell line (J. Interferon Cytokine Res., 2001, Antimicrob. Agents Chemother., 2002, 2005). The bacterial cytotoxicity correlates their virulence which is reported. In order to investigate the mechanisms of the cytotoxicity, biomedical and immunological character we investigate that the inducing activity of nitric oxide (NO) from human lung cell line A549 and the susceptibility to NO using twelve BCG strains. Among them three strains, Phipps, Russia and Japan, were observed inducing NO production from A549 higher than others. These strains are close to genetic background and exhibited synergistic effect of IL-1 and TNF-α on the NO production. Therefore, these strains may keep original characters of the primarily BCG vaccine and still have protective activity against Mycobacterium tuberculosis. On the other hand, in order to investigate the susceptibility to growth … More inhibitory or toxic effect of NO on bacteria, the twelve strains were cultured with Middlebrook 7H9 broth containing 10 % ADC and (0 to 1 mM) NaNO_2 for 21 days. Three BCG strains, Brazil, Glaxo and Russia, were very sensitive to NO, however, others were tolerant. The character to the susceptibility to NO did not correlate to the genetic background of BCG strains. NO tolerant strains may play a role in the survival in host and these strains could be useful for carrier of recombinant BCG vaccine in future.
A series of sugar derivatives were synthesized from stachyose, a sugar compound of Stachys sieboldi Miq, and evaluated for antibacterial activity against Mycobacterium tuberculosis, Mycobacterium avium, and Staphylococcus aureus, and their structure-activity relationships were studied. The results showed that the compound OCT359 (allyl O-(2,3,4,6-tetra-O-acetyl-α -Dgalactopyranosyl)-(1->6)-O-(2,3,4-tri-O-acetyl-a-D-galactopyranosyl)-(1->6)-0-2,3,4-tri-O-acetyl-β-D-glucopyranoside) exhibited in vitro antibacterial activity. The allyl group at C-1 and the acetoxy groups of the manniotrioside were requisite for the antibacterial activity. Less

  • Research Products

    (6 results)

All 2007 2005

All Journal Article (6 results)

  • [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, K. Onozaki
    • Journal Title

      Bioorg Med Chem Lett. 17

      Pages: 2487-2491

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Dihydroteststerone inhibits tumor necrosis factor alpha induced interleukin-l alpha 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., K.Onozaki
    • Journal Title

      Biol. Pharm. Bull. (In press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Study of susceptibility to nitric oxide among Mycobacterium bovis BCG strains and analysis of inducing activity of nitric oxide.2007

    • Author(s)
      Teki, T., Konodo, M., Kanai, K., Fujiwara, A., Yamamoto, S., Onozaki, K.
    • Journal Title

      BCG・BRM-ryoho-kennkyuukai-kaishi 29

      Pages: 3-8

    • Description
      「研究成果報告書概要(欧文)」より
  • [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, Teki T, Nishimura K, Yamamoto Y, Morikawa H, Abe C, K. Onozaki
    • Journal Title

      Bioorg Med Chem Lett. 17(9)

      Pages: 2487-2491

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Dihydroteststerone inhibits tumor necrosis factor alpha induced interleukin-1 alpha 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. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Mycobacterium bovis BCG亜株間の一酸化窒素(NO)感受性とNO産生誘導能の差異に関する研究2005

    • Author(s)
      瀧井猛将, 近藤真紀, 金井啓太, 藤原綾希子, 山本三郎, 小野嵜菊夫
    • Journal Title

      BCG ・ BRM療法研究会会誌 29

      Pages: 3-8

    • Description
      「研究成果報告書概要(和文)」より

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Published: 2008-05-27  

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