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1998 Fiscal Year Final Research Report Summary

Studies on regulatory mechanisms of LPS signal transductions in human cells.

Research Project

Project/Area Number 09670295
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Bacteriology (including Mycology)
Research InstitutionJichi Medical School

Principal Investigator

MATSUURA Motohiro  Jichi Medical School, Medical Department, Associate Professor, 医学部, 助教授 (20150089)

Co-Investigator(Kenkyū-buntansha) SAITO Shinji  Jichi Medical School, Medical Department, Research Associate, 医学部, 助手 (50195989)
Project Period (FY) 1997 – 1998
KeywordsEndotoxin / Lipopolysaccharide / LPS / Lipid A / TNF / IL-6 / Human macrophages
Research Abstract

The lipid A portion of bacterial LPS plays a central role in the production of endotoxic mediators. Different responses between human and murine macrophages to lipid A-like structures have been indicated. We investigated a series of structurally related monosaccharide lipid A analogues for their potency to activate human macrophage U937 cells and peripheral blood mononuclear cells for production of TNF-alpha and IL-6 compared with that of murine macrophage RAW264.7 cells. As the results, it was reveal that the structure of lipid A analogues recognized as LPS agonist by human cells comprises D-glucosamine, phosphoryl groups and acyl groups with defined carbon chain lengths of C14 and C12 in a ratio proportional to 1 : 1 : 3 ; these constituents are common to monosaccharide and disaccharide molecules and the elements necessary for recognition are more strict than those required by murine cells. In contrast, broad lipid A-like structures, which are recognized by the murine cells as LPS agonist and antagonist, are recognized as being LPS antagonist by human cells. It is now an important subject in LPS studies to find and characterize a putative LPS-receptor which transduces LPS-signals into cells. It is proposed that the protein recognizes lipid A-like structures in a productive or nonproductive manner for signal transduction and that the difference in this protein between animal species causes species specificity in the response of the cells to lipid A-like structures. In the present study, such a protein can be assumed to play a role as the target molecule for lipid A analogues to transduce their signals as LPS agonist or antagonist. Based on the information obtained in this study, further application of monosaccharide lipid A analogues as well as disaccharide analogues is promising in the search for valuable new information to elucidate of such problems.

  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Oda, T.: "Nitric Oxide-mediated modulation of interleukin-8 production by a human glioblastoma cell tine, T98G, cocultured with myeloid and monocytic cell line" J.Interferon Cytokine Res.18. 905-912 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Funatogawa, K.: "Relationship of structure and biological adivity to monosaccharide lipid A and logus to induction of nitric oxide production by murine macrophage RAW 264, 7 cells" Infect.Immun.66. 5792-5798 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tominaga, K.: "Lipopoiysaccharide tolerance in murine peritoneal macrophages induces downregulation of the LPS signal transduction pathwiy through MAPK and NF-xB cascades but not LPS incorporation steps" Biochim.Biophys.Acta. (in press). (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 松浦基博: "エンドトキシン研究シリーズ1.(LPS刺激によって誘導されるNO産生系へのIFN-γおよびIL-12の関与)" 近藤元治他編, 薬根出版, 5(p129-133) (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Oda, T.: "Nitric oxide-mediated modulation of interleukin-8 production by a human glioblastoma cell line, T98G,cocultured with myeloid and monocytic cell line." J.Interferon Cytokine Res.18. 905-912 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Funatogawa, K.: "Relationship of structure and biological activity to monosaccharide lipid A analogues to induction of nitric oxide production by murine macrophage RAW264.7 cells." Infect.Immun.66. 5792-5798 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tominaga, K.: "Lipopolysaccharide tolerance in murine macrophages induces downregulation of the LPS signal transduction pathway through MAPK and NF-kappaB cascades but not LPS incorporation." Biochim.Biophys.Acta. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsuura, M.: Participation of IFN-gamma and IL-12 on induction of NO production upon LPS stimulation. in Endotoxin Research Series 1 (in Japanese). Eds.Kondo, M.et al., Saikon Shuppan, 129-133 (1998)

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

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Published: 1999-12-08  

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