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Analysis of regulatory functions of immune system in breast-fed infants by TGF-beta in human milk-Basic study in various tissues of mice.

Research Project

Project/Area Number 10470180
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionNara Medical University

Principal Investigator

ISHIZAKA Shigeaki  Nara Medical University Medical School, Professor, 医学部, 教授 (90159715)

Co-Investigator(Kenkyū-buntansha) YOSHIKAWA Masahide  Nara Medical University, Medical School Associate Professor, 医学部, 助教授 (50230701)
SAITO Shigeru  Toyama Medical and Pharmaceutical University, Medical School, Professor, 医学部, 教授 (30175351)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 2000: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1999: ¥2,700,000 (Direct Cost: ¥2,700,000)
KeywordsTransforming growth factor-beta / Cytokine / Intestinal lymphocyte / Natural killer cell / Oral administration / mouse / ELISPOT / 腸管 / dendritic cells
Research Abstract

To investigate the effects of a large amount of transforming growth factor (TGF)-beta in human milk on immune system of breast-fed infants, mice received TGF-beta orally were examined. Interleukin(IL)-15 secretion in mouse intestinal epithelium was increased a short time after oral administration of TGF-beta. The increased IL-15 augmented natural killer (NK) cell activities in intraepithelial lymphocytes of intestine. In addition, the proliferation and activities of dendritic cell(DC) subtype 1 in intestinal intraepithelial lymphocytes were stimulated by IL-15 and subsequently IL-12 secretion from DC1 augmented. TH1 cells stimulated by IL-12 secreted remarkedly interferon(IFN)-gamma, suggesting that the increased IFN-gamma results in the augmentation of NK cell activities. NK cell activities in spleen enhanced several days after the augmentation in intestine.
TGF-beta, which contains in human milk, stimulated IL-15 secretion from intestinal epithelial cells. The increased IL-15 led to NK cell activities and IgA production not only in intestine but in various organs. In conclusion, oral administration of TGF-beta seems to be involved in early protection against infection with enteric or respiratory pathogens.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] S.Ishizaka: "Augmentation of natural killer cell activity in mice by oral administration of TGF-β."Immunology. 95. 460-465 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] S.Ishizaka: "Fosfomycin, an antibiotic, possessed of TGF-β-like immunoregulatory activities."Int.J.Immunopharmacol.. 20. 765-779 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 木本誠: "ホスホマイシンとTGF-β感受性"臨床免疫. 31(2). 202-208 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 豊原眞久: "Transforming growth factor-β(TGF-β)経口投与による生体内における抗体産生系の調節"消化器と免疫. 35. 57-60 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 吉川正英: "Transforming growth factor-β(TGF-β)のin vivo免疫調節作用-TGF-β経口投与の腸管リンパ球のサイトカイン産生に及ぼす影響"消化器と免疫. 36. 51-53 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 石坂重昭: "経口TGF-βによる腸管リンパ球のTh_1サイトカイン誘導"臨床免疫. (印刷中). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shigeaki Ishizaka: "Human antibodies and hybridomas"IOS Press. 85 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ishizaka, S., Kimoto, M., Kanda, S.and Saito, S.: "Augmentation of natural killer cell activity in mice by oral administration of transforming growth factor-beta."Immunology. 95. 460-465 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ishizaka, S., Takeuchi, H., Kimoto, M., Kanda, S.and Saito, S.: "Fosfomycin, an antibiotic, possessed TGF-beta-like immunoregulatory activities."Int.J.Immunopharmacol.. 20. 765-779 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Toychara, M., Yoshikawa, M., Kawamoto, H., Ueda, S., Kimoto, M., Yamao, J., Fukui, H.and Ishizaka, S.: "In vivo regulation of antibody production system by oral administration of transforming growth factor (TGF)-beta."Digest.Org.Mucos.Immunol.. 35. 57-60 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kimoto, M., and Ishizaka, S.: "The sensibility to TGF-beta augmented by fosfomycin."Clin.Immunol.. 31. 202-208 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yoshikawa, M., Kanda, S., Ueda, S., Toyohara, M., Takegami, T., Shiroi, K., Ishizaka, S.and Saito, S.: "In vivo immunoregulatory effects of transforming growth factor-beta(TGF-beta)-Effects of oral administration of TGF-beta on cytokine production in intestinal lymphocytes."Digest.org.Mucos.Immunol.. 36. 51-53 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yoshikawa, M., Ishizaka, S.and Saito, S.: "Augmentation of antibody production by oral administration of transforming growth factor(TGF)-beta."Human antibodies and Hybridoma. 85 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ishizaka, S., Kanda, M.and Yoshikawa, M.: "Induction of TH1-like cytokines in intraepithelial lymphocytes by oral administration of TGF-beta."Clin.Immunol.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 石坂重昭: "TGF-β経口投与による腸管NK細胞活性増強の機構"日本免疫学会学術集会記録. 30. 209 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 吉川正英: "TGF-β経口投与による肝臓内NK活性増強の機序"Minophagen Medical Review. (印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 石坂重昭: "経口TGF-βによる腸管リンパ球のTh_1サイトカイン誘導"臨床免疫. (印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shigeaki Ishizaka: "International conference on immunopharmacology"The international society of immunopharmacology. 51 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 豊原 眞久: "Transforming growth factor-β(TGF-β)経口投与による生体内における抗体産生系の調節"消化器と免疫. 35. 57-60 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 石坂 重昭: "TGF-βの経口投与による腸管サイトカイン産生の動態"日本免疫学会術集会記録. 29. 173 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 吉川 正英: "Transforming growth factor-β(TGF-β)のin vivo免疫調節作用-TGF-β経口投与の腸管リンパ球のサイトカイン産生に及ぼす影響"消化器と免疫. 36. 51-53 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shigeaki Ishizaka: "Human antibodies and hybridomas"IOS Press. 85 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] S.Ishizaka: "Augmentation of natural killer cell activity in mice by oral administration of TGF-β" Immunology. 95. 460-465 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shigeaki Ishizaka: "Fosfomycin,an antibiotic,possessed of TGF-β-like immunoregulatory activities" Int.J.Immunopharmacol.20. 765-779 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 木本 誠: "ホスホマイシンとTGF-β感受性" 臨床免疫. 31(2). 202-208 (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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