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Cellular and Molecular Analysis of the Relationship between Neuronal and Immune Systems

Research Project

Project/Area Number 09670688
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionOsaka University

Principal Investigator

YAMAMOTO Hiroshi  Graduate School of Pharmaceutical Sciences, Immunology, Osaka University, Professor, 薬学研究科, 教授 (50127312)

Co-Investigator(Kenkyū-buntansha) TSUJIKAWA Kazutake  Graduate School of Pharmaceutical Sciences, Immunology, Osaka University, Associate Professor, 薬学研究科, 助手 (10207376)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordsneuropeptide / T lymphocyte / neuro-immune interaction / cytokine / CGRP / NPY / サイトカイン / 神経ペプチド受容体 / 免疫制御 / ヘルパーT細胞 / ヘルパーT細胞サブセット / 神経-免疫連関 / T細胞サブセット
Research Abstract

Though immune outcome is known to be determined by which helper T cell response predominates, no local mechanism has yet been established which can explain how the neuronal system may control this. It is possible that the nervous system releases neuropeptides at specific local sites of infection or challenge, which triggers lymphocytes at those points to release specific cytokine profiles. These may then influence the direction of the Th1/Th2 response and therefore immune outcome. The aim of this study was to evaluate whether and if so how neuropeptides influence cytokine production by lymphocytes, especially T cells.
1 : We investigated the effects of two NPs, neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP), on the production of interferon-γ(IFNγ) and interleukin-4 (IL-4) by stimulating nonadherent splenocytes and helper T cell clones with antigens in vitro in the presence or absence of these peptides. NPY greatly enhanced IL-4 production and inhibited IFNγ. CGRP inhibited IFNγ production markedly in a dose-dependent manner, but had no effects on IL-4 production.
2 : Both NPY-and CGRP-receptors are expressed on the mouse T lymphocytes.
3 : Stimulation of T lymphocytes with two NPs resulted in an enhanced cAMP-mediated intracellular signaling process.
Therefore NPs directly act on T lymphocytes and can influence cytokine production. This opens the door to speculations that these specific cytokine profiles might play a part in influencing the direction of the consequent Th1/Th2 cascade and immune outcome and possibly the pathogenesis of immune-related diseases.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (35 results)

All Other

All Publications (35 results)

  • [Publications] Kawakami, Naoto: "Roles of integrins and CD44 on the adhesion and migration of fetal liver cells to the thymus"J. Immunol.. 163. 3211-3216 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kawakami, Naoto: "Green fluorescent protein-transgenic mouse : Immune functions and its application to the studies of lymphocyte development"Immunol. Lett.. 70. 165-171 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Miyazawa, Hitoshi: "Structure and promoter region of the surface membrane protein HS9 gene expressed on the thymic epithelial cells"Biochim. Biophys. Acta. 1444. 407-411 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kohama, Yasuhiro: "Immunostimulatory oligonucleotide induces Th-1 immune response and inhibition of IgE antibody production to ceder pollen allergens in mice"J. Allergy Clin. Immunol.. 104. 1231-1238 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamada, Eitaro: "Molecular cloning and characterization of a novel human STE20-like kinase, hSLK"Biochim. Biophys. Acta. (印刷中). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Iwao, Mutsumi: "Thymic atrophy in laminin-alpha-2 chain deficient mice is a result of selective death of CD4^+8^+ immature thymocytes"Immunology. (印刷中). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Matsuda, Y.: "Induction of myelin-associated glycoprotein expression through neuron-oligodendrocyte contact."Dev. Brain Research. 100. 110-116 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takeuchi, T.: "Transgenic expression of a novel thymic epithelial cell antigen stimulates aberrant development of thymocytes."J. Immunol.. 159. 726-733 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yoshida, Y.: "Antitumor effect of human pancreatic cancer cells transduced with cytokine genes which activate Th1 helper T cells."Anticancer Res.. 18. 333-336 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kawamura, N.: "Differential effects of neuropeptides on cytokine production by mouse helper T cell susets."NeuroImmunoModulation. 5. 9-15 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Iimori, H.: "Lateral hypothalamus modulates the intrinsic splenic natural killer cell activity in rats."NeuroImmunoModulation. 5. 221-225 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Miyazawa, H.: "Structure and promoter region of the surface membrane protein HS9 gene expressed on the thymic epithelial cells."Biochim. Biophys. Acta. 1444. 407-411 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hoq, Md. M.: "Insufficient resistance of trehalose-6, 6'-dimycolate-treated T-cell receptor δ gene mutant (TCRδィイD1-/-ィエD1) mice against influenza virus infection."Microbiol. Immunol.. 43. 491-493 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kawakami, N.: "Roles of integrins and CD44 on the adhesion and migration of fetal liver cells to the thymus."J. Immunol.. 163. 3211-3216 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kawakami, N.: "Green fluorescent protein-transgenic mouse : Immune functions and its application to the studies of lymphocyte development."Immunol. Lett.. 70. 165-171 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kohama, Y.: "Immunostimulatory oligonucleotide induces T helper-1 immune response and inhibition of IgE antibody production to cedar pollen allergens in mice."J. Allergy Clin. Immunol.. 104. 1231-1238 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamada, E.: "Molecular cloning and characterization of a novel human STE20-like kinase, hSLK."Biochim. Biophys. Acta. 14585. 1-13 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tasaki, K.: "Protective immunity is induced in murine colon carcinoma cells by the expression of interleukin-12 or interleukin-18 which activate Th1-type helper T cells."Cancer Gene Therapy. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yoshida, Y.: "Impaired tumorigenicity of human pancreatic cancer cells retrovirally transduced with interleukin-12 or interleukin-15 gene."Cancer Gene Therapy. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Iwao. M.: "Thymic atrophy in laminin-alpha-2 chain deficient mice is a result of selective death of CD4ィイD1+ィエD18ィイD1+ィエD1 immature thymocytes."Immunology. 99 (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Miyazawa Hitoshi: "Structure and promoter region of the surface membrane protein HS9 gene expressed on the thymic epithelial cells"Biochim.Biophys.Acta. 1444. 407-411 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kawakami Naoto: "Roles of integrins and CD44 on the adhesion and migration of fetal liver cells to the thymus"J.Immunol.. 163. 3211-3216 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kawakami Naoto: "Green fluorescent protein-transgenic mouse: Immune functions and its application to the studies of lymphocyte development"Immunol.Lett.. 70. 165-171 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kohama Yasuhiro: "Immunostimulatory oligonucleotide induces Th-1 immune response and inhibition of IgE antibody production to cedar pollen allergens in mice"J.Allergy Clin.Immunol.. 104. 1231-1238 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yamada Eitaro: "Molecular cloning and characterization of a novel human STE20-like kinase, hSLK."Biochim.Biophys.Acta. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Iwao Mutsumi: "Thymic atrophy in laminin-alpha-2 chain deficient mice is a result of selective death of CD4^+8^+ immature thymocytes"Immunology. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yoshida,Y., et al.: "Antitumor effect of human pancreatic cancer cells transduced with cytokine genes which activate Th1 helper T cells." Anticancer Research. 18. 333-336 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kawamura,N., et al.: "Differential effects of neuropeptides on cytokine production by mouse helper T cell subsets." NeuroImmunoModulation. 5. 9-15 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Iimori,H., et al.: "Lateral hypothalamus modulates the intrinsic splenic natural killer cell activity in rats." NeuroImmunoModulation. 5. 221-225 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Miyazawa,H., et al.: "Structure and promoter region of the surface membrane protein HS9 gene expressed on the thymic epithelial cells." Biochimica Biophysica Acta. in press. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Matsuda,Y.et al: "Induction of myelin-associated glycoprotein expression through neuron-oligodendrocyte contact." Developmental Brain Ressearch. 100. 110-116 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takeuchi,T.et al: "Transgenic expression of a novel thymic epithelial cell antigen stimulates aberrant development of thymocytes." Journal of Immunology. 159. 726-733 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yoshida,Y.et al: "Antitumor effect of human pancreatic cancer cells transduced with cytokine genes which activate Th1 helper T cells." Anticancer Research. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kawamura,N.et al: "Differential effects of neuropeptides on mouse T cell cytokine production." NeuroImmunoModulation. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Iimori,H.et al: "Lateral hypothalamus modulates the intrinsic splenic NK cell activity in rats." NeuroImmunoModulation. (in press). (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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