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Production of Cytokines After Stimulation of Bacterial Components And Protective Role of the Cytokines to Bacterial Infection

Research Project

Project/Area Number 01480180
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field 細菌学
Research InstitutionJichi Medical School

Principal Investigator

NAKANO Masayasu  Jichi Medical School, Microbiology, Prof., 医学部, 教授 (70048958)

Co-Investigator(Kenkyū-buntansha) NAKANO Yasunobu  Jichi Med. School, Microbiology, Instructor, 医学部, 助手 (70207851)
SHINOMIYA Hiroto  Jichi Med. School, Microbiology, Assistant Prof, 医学部, 講師 (80162618)
TAKI Tatsuo  Jichi Medical School, Microbiology, Assistant Pro, 医学部, 講師 (70049097)
Project Period (FY) 1989 – 1990
Project Status Completed (Fiscal Year 1990)
Budget Amount *help
¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 1990: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1989: ¥3,400,000 (Direct Cost: ¥3,400,000)
KeywordsLipopolysaccharide (LPS) / Cytokine / Protection against infection / Salmonella / Pseudomonas aeruginosa / 内毒素 / 菌体成分
Research Abstract

1. Mechanisms of macrophage activation by bacterial lipopolysaccharide (LPS). When murine peritoneal macrophages are stimulated by LPS, the macrophages produce various kinds of cytokines, and augment their bactericidal capacity. We investigated biochemical events in the macrophages after the stimulation of LPS. Calmodulin system was relevant to the macrophage activation by LPS to produce IL-1, while protein-kinase C and cyclic AMP as well as cyclic GMP seemed to be irrelevant to it. Shortly after LPS-stimulation, some proteins in the cell membrane and cytosol of the macrophages were phosphorylated. We purified the most dominant phosphorylated protein (pp65) in the cytosol, and found that the pp 65 was a substrate of serine kinase with a structure similar to human plastin.
2. Protective role of cytokines in the bacterial infection. When some of recombinant cytokines (either IFN-gamma, TNF-alpha and beta, IL-1, IL-6, or G-CSF) was injected into mice, bactericidal capacity and protectivity in the mice against Salmonella typhimurium (or S. enteritidis) and Pseudomonas aeruginosa were augmented. Combination of some of the cytokines or cytokine plus LPS was more effective. The augmentaion was partly due to the recruitment of phagocytic cells and the increment of the phagocytic and killing abilities of individual cells.

Report

(3 results)
  • 1990 Annual Research Report   Final Research Report Summary
  • 1989 Annual Research Report
  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Shinomiya,H.,Hirata,H.,and Nakano,M.: "Characterization and isolation of 65 kDa protein phosphorylated in murine macrophages by stimulation with bacterial lipopolysaccharide" J.Immunol.146. (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Nakano,Y.,Shirai,M.,Mori,N.,and Nakano,M.: "Neutralization of microcystin shock in mice by tumor necrosis factor alpha antiserum" Appl.Environ.Microbiol.57. 327-330 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Nakano,Y.,Onozuka,K.,Terada,Y.,Shinomiya,H.,and Nakano,M.: "Protective effect of recombinant tumor necrosis factorーα in murine salmonellosis" J.Immunol.144. 1935-1941 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Nakano,M.,Terada,Y.,Matsumura,H.,and Shinomiya,H.: "Possible refractory site on LPSーinduced interleukin 1 production in C3H/HeJ peritoneal macrophages" Advances in experimental medicine and biology. 256. 347-359 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Matsumura,H.,Onozuka,K.,Terada,Y.,Nakano,Y.,and Nakano,M.: "Effect of murine recombinant interferonーγ in the protection of mice against salmonella" Int.J.Immunopharmac.12. 49-65 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Nakano,M.,and Shinomiya,H.: "Cellular and Molecular Aspects of Endotoxin Reaction (pp.205ー214,Molecular mechanisms of macrophage actevation by LPS)" Editors:Nowotny,A.,et al.Publisher:Elsevier,Amsterdem, (566)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Friedman,H.,Klein,T.W.,Nakano,M.,and Nowotny,A.: "Endotoxin" Plenum Press,New York, 715 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Shinomiya, H., Hirata, H., and Nakano, M.: "Characterization ans isolation of 65kDa protein phosphorylated in murine macrophages by stimulation with bacterial lipopolysaccharide." J. Immunol. 146. (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Nakano, M., Onozuka, K., Sakamoto, K., Nakano, Y., Shinomiya, H., and Saito-Taki, T.: "Protective effect of cytokines in mice to Pseudomonas aeruginosa-infection." Proceedings of the 3rd International Symposium on Basic Research and Clinical Aspects of Pseudomonas aeruginosa Infection (Eds. by Holder, I. A., et al.), Karger, Basel, 1991.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Nakano, Y., Shirai, M., Mori, N., and Nakano, M.: "Neutralization of microcystin shock in mice by tumor necrosis factor alpha antiserum." Appl. Environ. Microbiol. 57. 327-330 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Nakano, M., and Shinomiya, H.: "Molecular mechanisms of macrophage activation by LPS." Cellular and Molecular Aspects of Endotoxin Reactions (Eds. by Nowotny, A., et al.). 205-214 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Nakano, Y., Onozuka, K., Terada, Y., Shinomiya, H., and Nakano, M.: "Protective effect of recombinant tumor necrosis factor-alpha in murine salmonellosis." J. Immunol.144. 1935-1941 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Nakano, M., Terada, Y., Matsumura, H., and Shinomiya, H.: "Possible refractory site on LPS-induced interleukin 1 production in C3H/HeJ peritoneal macrophages." Advances in Experimental Medicine and Biology. 256. 347-359 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Matsumura, H., Onozuka, K., Terada, Y., Nakano, Y., and Nakano M.: "Effect of murine recombinant interferon-gamma in the protection of mice against salmonella." Int. J. Immnuopharmac. 12. 49-65 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Friedman, H., Klein, T. W., Nakano, M., and Nowotny, A.: Plenum Press, New York. Endotoxin (Advances in Experimental Medicine and Biology, Vol. 256), 1-715 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Shinomiya,H.,Hirata,H.,and Nakano,M.: "Characterization and isolation of 65 kDa protein phosphorylated in murine macrophages by stimulation with bacterial lipopolyーsaccharide" J.Immunol.146. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Nakano,Y.,Shirai,M.,Mori,N.,and Nakano,M.: "Neutralization of microcystin shock in mice by tumor necrosis factor alpha antiserum" Appl.Environ.Microbiol.57. 327-330 (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Nakano,Y.,Onozuka,K.,Terada,Y.,Shinomiya,H.,and Nakano,M.: "Protective effect of recombinant tumor necrosis factorーα in murine salmonellosis" J.Immunol.144. 1935-1941 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Nakano,M.,Onozuka,K.,Sakamoto,K.,Nakano,Y.,Shinomiya,H.,and SaitoーTaki,T.: "Proceedings of the 3rd International Symposium on Basic Research and Clinical Aspects of <Pseudomonas>___ー <aeruginosa>___ー Infection" Editors:Hold,I.A.,et al.Publisher:Karger,Basel, (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Nakano,M.,and Shinomiya,H.: "Cellular and Molecular Aspects of Endotoxin Reactions(pp.205ー214,Molecular mechanisms of macrophage activation by LPS)" Editors:Nowotny,A.,et al.Publisher:Elsevier,Amsterdam, 566 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 四宮博人: "エンドトキシンの細胞内シグナル伝達" 化学療法の領域. 15. 47-53 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 中野昌康: "マクロファ-ジの産生する活性物質" 日本臨牀. 47. 526-533 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] M.Nakano: "Toxicity of Microcytis aeruginosa K-139 strain" Microbiology and Immnology. 33. 789-792 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] H.Matsumura: "Effect of murine recombinant interferon-γ in the protection of mice against Salmonella" International Journal of Immunopharmacology. 12. 49-65 (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] M.Nakano: "Possible refractory site on LPS-induced interleukin 1 production in C3H/HeJ peritoneal macrophages" Advances in Experimental Medicine and Biology. 256. 347-359 (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] Y.Nakano: "Protective effect of recombinant tumor necrosis factor-α in murine salmonellosis" Journal of Immunology. 144. (1990)

    • Related Report
      1989 Annual Research Report

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Published: 1989-04-01   Modified: 2016-04-21  

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