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Establishment of an immunoassay system for monocyte chemotacticand activating factor (MCAF) and its clinical application

Research Project

Project/Area Number 04671430
Research Category

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

Allocation TypeSingle-year Grants
Research Field Laboratory medicine
Research InstitutionKanazawa University

Principal Investigator

MUKAIDA Naofumi  Department of Pharmacology, cancer Research Institute, Kanazawa University, Associate Professor, がん研究所, 助教授 (30182067)

Co-Investigator(Kenkyū-buntansha) KAWAI Tadashi  Department of Clinical Pathology, Jichi Medical School, Professor, 医学部, 教授 (60048957)
Project Period (FY) 1992 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1993: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1992: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywordscytokine / chemokine / enzyme-linked immunosorbent assay / interleukin / monocyte chemotactic and activating factor / サイトカイニン / 尿路感染症 / 髄膜炎
Research Abstract

The results of the project is summarized as follows.
1. We established MCAF-producing cell line by transfecting MCAF cDNA into a mouse myeloma cell line and purified MCAF from the culture supernatants of this cell line. We observed that the preadministration of purified recombinant MCAF could prevent either normal or granulocytopenic mice from lethal infection caused by pseudomonas aeruginosa o r Salmonella typhymurium.
2. We established a specific and sensitive ELASA against human MCAF.Using this ELASA, we observed that the pleural fluid levels of MCAF increased in patients with malignant pleurisy upon the administration of an immunomodulator, OK-432. In addition, most human glioblastoma cell lines could produce MCAF in response to IL-1 or TNFalpha, suggesting a potential role of MCAF in tumor immunity.
3. We also examined the role of MCAF-related molecule, interleukin-8 (IL-8) in the acute inflammation by administering a neutralizing antibody against IL-8. these experiments demonstrated that IL-8 plays an essential role in neutrophil infiltration and neutrophi-dependent tissue injuries in lipopolysaccharide-induced dermatitis and lung reperfusion injury.
4. The determination of urinary IL-8 lavels using ELISA revealed that urinary IL-8 levels increased in the urines of patients with urinary tract infections and those with several types of glomerulonephritis such as lupus nephritis, acute glomerulonephritis, and IgA nephropathy with acute exacerbations.
These results imply that the determination of urinary IL-8 level can be used for diagnosing and monitoring several diseases in urinary tracts.
In addition, we explored the molecular biological aspects of IL-8 gene activation and established that NF_<-k>B site was essentially involved in the transcription of IL-8 gene in every cell line that we examined.

Report

(3 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Ko,Y.-C.,Mukaida,N.,Panyutich,A.et al.: "A sensitive enzyme-linked immunosorbent assay for human interleukin 8." Journal of Immunological Methods. 149. 227-235 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yasumoto,K.,Okamoto,S.-i.,Mukaida,N.,et al.: "Tumor necrosis factor α and interferon γ synergistically induce interleukin 8 production in a human gastric cancer cell line through acting concurrently on AP-1 and NF-kB like binding sites of the interleukin 8 gene." Journal of Biological Chemistry. 267. 22506-22511 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ko,Y.-C.,Mukaida,N.,Ishiyama,S.,et al.: "Elevated IL-8 level in the urine of patients with urinary tract infections." Infection and Immunity. 61. 1307-1314 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sekido,N.,Mukaida,N.,Harada,A.,et al.: "Prevention of lung reperfusion injury in rabbits by a monoclonal antibody against interleukin-8." Nature. 365. 654-657 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Morita,M.,Kasahara,T.,Mukaida,N.,et al.: "Induction and regulation of IL-8 and MCAF production in human brain tumor cell lines and brain tumor tissues." European Cytokine Network. 4. 351-358 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Nakano,Y.,Kasahara,T.,Mukaida,N.,et al.: "Prevention of fatal bacterial infection in mice by monocyte chemotactic and activating factor(MCAF)." Infection and Immunity. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] KO, Y-C., Mukaida, N., Panuytich, A., voitenok, N.N., Matsushima, K., kawai, T., and kasahara, T.: "A sensitive enzyme-linked immunosorbent assay for human interleukin-8" Journalof Immunological Methods. 149. 227-235 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Okutani, R., Itoh, Y., Hirata, H., Kasahara, T., Mukaida, N., and Kawai, T.: "Simple and high-yield purification of urine protein 1 using immunoaffinity chromatography : evidence for the identity of urine protein 1 and human Clara cell 10-kilodalton protein" Journal of Chromatography. 577. 25-35 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mukaida, N., Gusella, G.L., Kasahara, T., Ko, Y.-C., Zachariae, C.O.C., kawai, T., and Matsushima, K.: "Molecular analysis of the inhibition of interleukin-8 production by dexamethasone in a human fibrosarcoma cell line" Immunology. 75. 674-679 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mukaida, N., Morimoto, T., Takanashi, N., and Kawai, T.: "Establishment of a sensitive radioimmunoassay for serum thymic factor wth a special reference to extraction procedures" Journal of Clinical Laboratory Analysis. 6. 30-34 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yasumoto, K., Okamoto, S.-i, Mukaida, N., Murakami, S., Mai, M., Matsushima, K.: "Tumor necrosis factor alpha and interferon gamma synergistically induce interleukin 8 production in a humangastric cancer cell line through acting concurrently on AP-1 and NF-kB binding sites of the interleukin 8 gene" Journal of Biological Chemistry. 267. 22506-22511 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ko, Y.-C., Mukaida, N., Ishiyama, S., Tokue, A., Kawai, T.Matsushima, K.and kasahara, T.: "Elevated interleukin-8 levels in the urine of patients with urinary track infections" Infection and Immunity. 61. 1307-1314 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] harada, A., Sekida, N., Kuno, K., Akiyama, M., Kasahara, T., nakanishi, I., Mukaida, N., and Matsushima, K.: "Expression of recombinant rabbit IL-8 in Escherichia coli and establishment of the ssential involvement of IL-8 in recruiting neutrophils into lioppolysaccharide-induced inflammatory site of rabbit skin." International Immunology. 5. 681-690 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Tsuchiya, I., Kasahara, T., Yamahsita, K., Ko, Y.-C., Kanazawa, K., Matsushima, K., and Mukaida, N.: "Induction of inflammatory cytokines in the pleural effusion of cancer patients after the administration of an immunomodulator, OK-432 : role of IL-8 for neutrophil infiltration" Cytokine. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Horiguchi, H., Mukaida, H., Okamoto, S.-i, Teranishi, H., Kasuya, M., and Matsushima, K.: "Cadmium induces interleukin-8 production in human peripheral blood mononuclear cells with the concomitant generation of superoxide radicals" Lymphokine and Cytokine Research. 12. 421-428 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Matsukawa, T., Fujikawa, K., Nishio, Y., Mukaida, N., Matsushima, K., Kishimoto, T., and Akira, S.: "Transcription factors NF-IL6 and NF-kB synergistically activate transcription of the inflammatory cytokines, interleukin 6 and interleukin 8" Proceedings of national Academy of Science U.S.A.90. 10193-10197 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Morita, M., Kasahara, T., Mukaida, N., Matsushima, K., Nagashima, T., Nishizawa, M., and Yoshida, M.: "Induction and regulation of IL-8 and MCAF production in human brain tumor cell lines and brain tumor tissues" European Cytokine Network. 4. 351-358 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Nakano, Y., Kasahara, T., Mukaida, N., Ko, Y.-C., Nakano, M., and Matsushima, K.: "Protection of lethal bacterial infection in mice by monocyte chemotactic and activating factor (MCAF)" Infection and Immunity. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Harada, A., Kuno, K., Nomura, H., Mukaida, N., Murakami, S., and Matsushima, K.: "Molecular cloning of cDNA encoding mouse interleukin-8 (IL-8) receptor" Gene. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ko,Y.-C.,Mukaida,N.,Ishiyama,S.,et al.: "Elevated IL-8 level in the urine of patients with urinary tract infections." Infection and Immunity. 61. 1307-1314 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Sekido,N.,Mukaida,N.,Harada,A.,et al.: "Prevention of lung repertusion injury in rabbits by a monoclonal antibody against interleukin-8." Nature. 365. 654-657 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Matsusaka,T.,Fujikawa,K.,Nishio,Y.,Mukaida,N.,et al.: "Transcription factors NF-IL6 and NF-kB synergistically activate transcription of the inflammatory cytokines,interleukin 6 and interleukin 8." Proceedings of National Academy of Science U.S.A.90. 10193-10197 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Morita,M.,Kasahara,T.,Mukaida,N.,et al.: "Induction and regulation of IL-8 and MCAF production in human brain tumor cell lines and brain tumor tissues." European Cytokine Network. 4. 351-358 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Nakano,Y.,Kasahara,T.,Mukaida,N.,et al.: "Prevention of fatal bacterial infection in mice by monocyte chemotactic and activating factor(MCAF)." Infection and Immunity. (印刷中).

    • Related Report
      1993 Annual Research Report
  • [Publications] Matsushima,K & Mukaida,N.: "Interleukin-8 and MCAF:novel leukocyte recrutiment and activating cytokines." Chemical Immunology. 51. 236-265 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 向田 直史: "単球走化活性化因子(MCAF)の産生調節機構" 臨床免疫. 24. 840-848 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Mukaida,N.,Harada,A.,Yasumoto,K.& Matsushima,K.: "Properties of pro-inflam matory cell type-specific leukocyte chemotactic cytokines,interleukin 8(IL-8)and monocyte chemotactic and activating factor" Microbiology and Immunology. 36. 773-789 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Ko,Y.-C.,Mukaida,N.,Ishiyama,S.,Tokue,A.,Kawai,T.,Matsushima.K.& Kasahara.T.: "Elevated IL-8 level in the urine of patients with urinary tract infection" Infection and Immunity. (1993)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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