1993 Fiscal Year Final Research Report Summary
Establishment of an immunoassay system for monocyte chemotacticand activating factor (MCAF) and its clinical application
| Project/Area Number |
04671430
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Laboratory medicine
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| Research Institution | Kanazawa University |
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Principal Investigator |
MUKAIDA Naofumi Department of Pharmacology, cancer Research Institute, Kanazawa University, Associate Professor, がん研究所, 助教授 (30182067)
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| Co-Investigator(Kenkyū-buntansha) |
KAWAI Tadashi Department of Clinical Pathology, Jichi Medical School, Professor, 医学部, 教授 (60048957)
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| Project Period (FY) |
1992 – 1993
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| Keywords | cytokine / chemokine / enzyme-linked immunosorbent assay / interleukin / monocyte chemotactic and activating factor |
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| 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.
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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[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)
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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[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).
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[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)
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[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)
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[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)
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[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).
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[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).
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