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Expression and Regulation of Inflammatory Cytokine Genes In Vitro and In Vivo

Research Project

Project/Area Number 04671366
Research Category

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

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionJichi Medical School, Department of Medicine Grant-in-Aid for Scientific Research(C)

Principal Investigator

KASAHARA Tadashi  Jichi Med.Sch., Dept.Med., Assoc.Prof., 医学部, 助教授 (60049096)

Co-Investigator(Kenkyū-buntansha) 高 余洲  自治医科大学, 医学部, 助手 (30234686)
MUKAIDA Naofumi (YUE CHOU Ko)  Kanazawa Univ., Cancer Inst., Assoc.Prof., がん研究所, 助教授 (30182067)
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)
KeywordsInflammatory cytokine / IL-8 / MCAF / gene regulation / neutrophil chemotaxis / in vivo effect / 1L-8 / ケモタキシス
Research Abstract

We investigated the in vitro and in vivo role of inflammatory cytokines, IL-8 and MCAF with neutrophil and monocyte chemotactic activities, which is induced rapidly by the stimulation of IL-1 or TNF.Our results indicate that
(1) Induction of IL-8 and MCAF Genes in Various Tumor Cell Lines and Its Regulation by Glucocorticoid : Fibrosarcoma and glioblastoma cell lines were found to express high levels of these inflammatory cytokines genes. The regulatory elements in IL-8 gene and nuclear factors (NF-kB, C/EBP, AP-1) were identified, particularly in interests of glucocorticoid action (Mukaida et al. Immunol.1992 ; Eur.Cytok, Netw 1993 ; J.Biol.Chem.1994 in press).
(2) Determination of Inflammatory Cytokines In Various Disease States : Production of IL-8 and MCAF in various infectious and inflammatory diseases were determined using ELISA methods. Significant levels of IL-8 was observed in urines from urinary tract infection and amniotic fluids from pregnant women. Similarly, significant levels of IL-8 were detected in synovial fluids from rheumatoid arthritis or pleural fluids from cancer patients, providing valuable monitoring in these inflammatory responses.(Saito et al. Cytokine 1993 ; Ko et al. Infect. Immunity 1993 ; Tsuchiya et al.Cytokine 1993)
(3) Large-scale Production of MCAF and In Vivo Application : Administration of MCAF was found to be effective to protect mice from lethal Salmonella and Pseudomonas infection in vivo (Nakano et al.Infect.Immun.1994)

Report

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

    (62 results)

All Other

All Publications (62 results)

  • [Publications] Ko,Y-C.: "Establishment of a sensitive enzyme-linked immunosorbent assay for human IL-8" J.Immunol.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] Mukaida,N.: "Molecular analysis of the inhibition of IL-8 production by dexamethasone in a human fibrosar coma cell line." Immunology. 75. 674-679 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ikeda,U.: "Serum interleukin 6 levels become elevated in acute myocardial infarction." J.Mol.Cell.Cardiol.24. 579-584 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Takeda,Y.: "Lobenzarit disodium (CCA) inhibits in vitro immunoglobulin production via direct interaction with B lymphocytes" Chem.Pharm.Bull.40. 177-181 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kikuchi,Y.: "Induction of metallothionein in a human astrocytoma cell line by interleukin-1 and heavy metals." FEBS Letters. 317. 22-26 (1993)

    • 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.: "Elevated IL-8 level in the urine of patients with urinary tact infections." Infect.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] Saito,S.: "Elevation of amniotic fluid IL-6,IL-8 and granulocyte-colony stimulating factor (G-CSF) in term and preterm parturition." Cytokine. 5. 81-88 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sato,K.: "Passive immunization with anti-parathyroid hormone-related protein monoclonal antibody markedly prolongs survival time of" J.Bone Mineral Res.8. 849-860 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Harada,A.: "Expression of recombinant rabbit IL-8 in Escherichia coli and estabilishment of the essntial involvement of IL-8 in recruiting" Intl.Immunol.5. 681-690 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ikeda,U.: "Expression of intercellular adhesion molecule-1 on rat vascular smooth muscle cells by proinflammatory cytokines." Atherosclerosis. 104. 61-68 (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.: "Induction and regulation of IL-8 and MCAF mRNA expression in human glioblastoma and neuroblastoma cell lines." Eur.Cytokine Netw.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] Tsuchiya,I: "Induction of inflammatory cytokines in the pleural effusion of cancer patients afterthe administration of an immunomodulator" Cytokine. (in press). (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.: "Protection of lethal bacterial infection in mice by monocyte chemotactic and activating factor(MCAF)." Infect.Immunity. (in press). (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mukaida,N.: "A novel mechanism of glucocorticoid-mediated gene repression:NF-kB is the target for glucocorticoid-mediated IL-8 gene repression." J.Biol.Chem.(in press). (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sawada,J-I.: "Induction of metallothionein in astrocytes by cytokines and heavy metals." Biological Signals. (in press). (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Nielsen,B.W.: "Macrophage-Pathogen Interactions" Marcel-Dekker,New York,ed.by Zwillin,B.S.et al., 131-142 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hatake,K.: "Molecular Biology of Haematopoiesis" Intercept Ltd.,Hampshire,ed.by N.G.Abraham,et al., 127-133 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 笠原 忠: "「生体防御」(Maruzen Advanced Technology)" 新井賢一編、丸善、東京, 95-103 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 笠原 忠: "サイトカインと疾病" 笠倉新平編、日本医学館,東京, 177-185 (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., Panyutich, A., Voitenek, N.K., Matsushima, K., Kawai, T., Kasahara, T.: "Establishment of a sensitive enzyme-linked immunosorbent assay for human IL-8." J.Immunol.Meth.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] Mukaida, N., Gusella, G.L., Kasahara, T., Ko, Y., Zacchariae, C.O., Kawai, T., Matsushima, K.: "Molecular analysis of the inhibitin of IL-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] Ikeda, U., Ohkawa, F., Seino, Y., Yamamoto, K., Hikaka, Y., Kasahara, T., Kawai, T., Shimada, K.: "Serum interleukin 6 levels become elevated in acute myocardial infarction." J.Mol.Cell.Cardiol.24. 579-584 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Takeda, Y., Urakawa, K., Sakamoto, A., Nakano, T., Sugawara, Y., Ohsugi, Y., Morita, M.and Kasahara, T.: "Lobenzarit disodium (CCA) inhibits in vitro immunoglobulin production via direct interaction with B lymphocytes." Chem.Pharm.Bull.40. 177-181 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kikuchi, Y., Irie, M., Kasahara, T., Sawada, J-I., Terao, T.: "Induction of metallothionein in a human astrocytoma cell line by interleukin-1 and heavy metals." FEBS Letters. 317. 22-26 (1993)

    • 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., Kasahara, T.: "Elevated IL-8 level in the urine of patients with urinary tract infections." Infect.Immun.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] Saito, S., Kasahara, T., Kato, Y., Ishihara, Y.and Ichijo, M.: "Elevation of amniotic fluid IL-6, IL-8 and G-CSF in term and preterm parturition." Cytokine. 5. 81-88 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sato, K., Yamakawa, Y., Shizume, K., Sato, T., Nohtomi, K., Demura, H., Akatsu, Y., Nagata, N., Kasahara, T., et al.: "Passive immunization with anti-parathyroid hormonerelated protein monoclonal antibody markedly..." J.Bone Mineral Res.8. 849-860 (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., Sekido, N., Kuno, K., Akiyama, M., Kasahara, T., Nakanishi, I., Mukaida, N., Matsushima, K.: "Expression of recombinant rabbit IL-8 in Escherichia coli and establishment of the essential involvement of IL-8..." Intl.Immunol.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] Ikeda, U., Ikeda, M., Seino, Y., Takahashi, M., Kasahara, T., Kano, S., Shimada, K.: "Expression of intercellular adhesion molecule-1 on rat vascular smooth muscle cells by proinflammatory cytokines." Atherosclerosis. 104. 61-68 (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., Nishizawa, M., Yoshida, M.: "Induction and regulation of IL-8 and MCAF mRNA expression in human glioblastoma and neuroblastoma cell lines." Eur.Cytokine Net.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] Tsuchiya, I., Kasahara, T., Yamashita, K., Ko, Y-C, Kanazawa, K., Matsushima, K., 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. 5. 595-603 (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., Ko, Y-C., Mukaida, N., et al.: "Protection of lethal bacterial infection in mice by monocyte chemotactic and activating factor (MCAF)." Infect.Immun.in press. (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mukaida, N., Morita, M., Ishikawa, Y., Rice, N., Okamoto, S., Kasahara, T., Matsushima, K.: "A novel mechanism of glucocorticoid-mediated gene repression : NF-kB is the target for glucocorticoid-mediated IL-8 gene repression." J.Biol.Chem.in press. (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Saito, S., Kasahara, T., Sakakura, S., Enomoto, M., Umekage, H., et al.: "IL-8 production by CD16^-CD56^<bright> natural killer cells in the human early pregnancy decidua." B.B.R.C.in press. (1994)

    • 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.: "Establishment of a sensitive enzyme-linked immunosorbent assay for human IL-8" J.Immunol.Methods. 149. 227-235 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] Mukaida,N.: "Molecular analysis of the inhibition of IL-8 production by dexamethasone in a human fibrosar coma cell line." Immunology. 75. 674-679 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ikeda,U.: "Serum interleukin 6 levels becoe elevated in acute myocardial infarction." J.Mol.Cell.Cardiol.24. 579-584 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] Takeda,Y.: "Lobenzarit disodium (CCA)inhibits in vito immunoglobulin production via direct interaction with B lymphocytes" Chem.Pharm.Bull.40. 177-181 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kikuchi,Y.: "Induction of metallothionein in a human astrocytoma cell Iine by interleukin-1 and heavy metals." FEBS Letters. 317. 22-26 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ko,Y-C.: "Elevated IL-8 level in the urine of patients with urinary tact infections." Infect.Immunity. 61. 1307-1314 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Saito,S.: "Elevation of amniotic fluid IL-6,IL-8 and granulocyte-colonystimulating factor (G-CSF)in term and preterm parturition." Cytokine. 5. 81-88 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Sato,K.: "Passive immunization with anti-parathyroid hormone-related protein monoclonal antiboby markedly prolongs survival time of" J.Bone Mineral Res.8. 849-860 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Harada,A.: "Expression of recombinant rabbit IL-8 in Escherichia coli and estabilishment of the essential involvement of IL-8 in rocruiting" Intl.Immunol.5. 681-690 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ikeda,U.: "Expression of intercellular adhesion molecule-1 on rat vascular smooth muscle cells by proinflammatory cytokines." Atherosclerosis. 104. 61-68 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Morita,M.: "Induction and regulation of IL-8 and MCAF mRNAexpression in human glioblastoma and neuroblastoma cell Iines." Eur.Cytokine Netw.4. 351-358 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tsuchiya,I,: "Induction of inflammatory cytokines in the pleural effusion of cancer patients after the administration of an immunomodulator," Cytokine. (in press). (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Nakano,Y.,: "Protection of lethal bacterial infection in mice by monocyte chemotactic and activating factor(MCAF)." Infect. Immunity. (in press). (1994.)

    • Related Report
      1993 Annual Research Report
  • [Publications] Mukaida,N.,: "A novel mechanism of glucocorticoid-mediated gene repression: NF-kB is the target for glucocorticoid-mediated IL-8 gene repression." J.Biol.Chem.(in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Sawada,J-I.: "Induction of metallothionein in by cytokines and heavy metalsx" Biological Signals. (in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Nielsen,B.W.: "Macrophage-Pathogen Interactions" Marcel-Dekker,New York,ed.by Zwillin,B.S.et al., 131-142 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hatake,K.: "Molecular Biology Haematopoiesis" Inercept Lyd.Hampshire,ed.by N.G.Abraham,et al.,

    • Related Report
      1993 Annual Research Report
  • [Publications] 笠原 忠: "「生体防御」(Maruzen Advanced Technology)" 新井賢一編、丸善、東京, p.95-103, (1992.)

    • Related Report
      1993 Annual Research Report
  • [Publications] 笠原 忠: "「生体防御」(Maruzen Advanced Technology)" 新井賢一編、丸善、東京, p.95-103, (1992.)

    • Related Report
      1993 Annual Research Report
  • [Publications] 笠原 忠: "「サイトカインと疾病」" 笠倉新平編、日本医学館、東京, p.177-185, (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ko,Y-C. Mukaida,N.Kasahara,T.et al.: "Establishment of a sensitive enzyme-linked immunosorbent assay for human 1L-8." J.lmmunol.Methods. 149. 227-235 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Mukaida,N. Gusella, G.,Kasahara,T.Ko, Y-C.,et al.: "Molecular analysis of the inhibition of 1L-8 production by dexamethasone in a human fibrosarcoma cell line." Immunology. 75. 674-679 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Ikeda,U.Ohkawa, F kasahara,T.et al.: "Serum interleukin 6 levels become elevated in acute myocardial infarction." J.Mol.Cell.Cardiol.24. 579-584 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Saito,S. Kasahara, T.,kato, Y.et al.: "Elevation of amniotic fluid interleukin-6 IL-8 and granulocyte-colony stimulating factor in term and preterm parturition." Cytokine. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kikuchi, Y.Irie, M.Kasahara, T.et al.: "Induction of metallothionein in a human astrpcytoma cell line by interleukin-1 and heavy metals." FEBS Letters. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Ko,Y-C.MuKaida, N.Kasahara,T.et al.: "Elevated IL-8 level in the urine of patients with urinary tract infections." Infection Immunity. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Nielsen,B.W.Mukaida,N. Kasahara,T.Matsushima,K.: "“Macrophage-Pathogen Interactions"" Marcel-Dekker,(1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] 笠原 忠(分担): "「サイトカインと疾病」(笠倉新平編)" 日本医学館, 6 (1992)

    • Related Report
      1992 Annual Research Report

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

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