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(Specific Regulation of Mechanism of Hypercalcemia Induction in Adult T Cell Leukemia.)

Research Project

Project/Area Number 09470226
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 内分泌・代謝学
Research InstitutionUniversity of Occupational and Environmental Health

Principal Investigator

ETO Sumiya  Scl.of Med.University of Occupational and Environmental Health Professor, 医学部, 教授 (90010347)

Co-Investigator(Kenkyū-buntansha) TUKADA Junichi  Scl.of Med. University of Occupational and Environmental Health Lecturer, 医学部, 助手 (20227367)
MORIMOTO Isao  Scl.of Med.University of Occupational and Environmental Health Associate Prof., 医学部, 助教授 (80145234)
TANAKA Yoshiya  Scl.of Med.University of Occupational and Environmental Health Assist.Prof., 医学部, 講師 (30248562)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥8,200,000 (Direct Cost: ¥8,200,000)
Fiscal Year 1998: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1997: ¥5,200,000 (Direct Cost: ¥5,200,000)
KeywordsATL / Hypercalcemia / Cell Adhesion Molecules / IL-1 gene / TAX protein / TAX蛋白 / 細胞接着 / LFA-1 / イソテグン / G蛋白 / Tax蛋白 / IL-1β遺伝子 / 核内転写因子
Research Abstract

I.Results related with IL-1 (Bone resorption activating factor) gene Insertion of Human IL-1beta gene promotor fragmen with TAX protein which is producted by HTLV- I infection to Jurkat cells ; not HTLV-I infected T cell leukemia (ATL model) increased IL-1beta gene activity assayed by CAT compared with non- inserted cells. When the binding site in gene promortor of NF-IL6 or SP-1 which are the IL-1beta gene transactivators was muteted, this increse was completely blocked.
Insertion of Human IL-1alpha cx gene promotor fragment with TAX protein also incresed IL-1alpha a gene activity. In this case, this increase was blocked by the mutation of binding site of NF- Kbeta which is the IL-1alpha gene transactivator.
These results sugest that TAX protein is strongly involved with the production of IL-1, and the binding of NF-IL6, SP-1, NF-Kbeta to IL-1 gene promortor is essential for induction of IL-1 by TAX protein.
II.Result related with adhesion molecules
It is known that bone resorption is induced through osteoblast. Heterotypic adhesion of ATL cells and HOS cells ; osteoblast cell line, increased the expression of IL-1 mRNA in HOS cells and production of IL-1beta from HOS cells. In addition, this mRNA expression and protein production was significantly decreased by adding anti-VLA-4, LFA-1 antibody.
Theses results sugest that adhesion of ATL cells and osteoblast through various adhesion molecules is also essential for producton of IL-1.

Report

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

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Okada, Yousuke: "Short term treatment of recombinant murine interleukin-4 rapidly inhibits bone formation in normal and overiectomized mice." Bone. 22. 361-368 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tanaka, Yoshiya: "Constitutive chemokine production results in activation of leukocyte function-associated antigen-1 on adult T cell lekemia cells." Blood. 91. 3309-3919 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tanaka, Yoshiya: "Modulation of cytokine function by heparan sulfate proteoglycans : sophisticated models for the regulation of cellular responses to cytokines." Proc.Assoc.Am.Physicians. 110. 118-125 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tsukada, Junichi: "Human T-cell leukemia virus type I tax transactivates the promortor of human prointerleukin-β gene through association with two transcription factors, nuclear factor - interleukin-6 and Spi-1." Blood. 90. 3142-3153 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Isida, Osamu: "Chondrocyte are regulated by cellular adhesion through CD44 and hyalronic acid pathway." J.Bone Miner.Res.12. 1657-1663 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mori, Naoki: "Characterization and regulation of interleukin-4 receptor in adult T cell leukemia cells." Eur.J.Haematol.56. 241-247 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tanaka, Yoshiya: "Constitutive chemokine production results in activation of leukocyte function-associated antigen-1 on adult T cell lekemia cells." Blood. 91. 3309-3919 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Okadda, Yosuke: "Short term treatment of recombinant murine interleukin-4 rapidly inhibits bone formation in normal and overiectomized mice." Bone. 22. 361-368 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tanaka, Yoshiya: "Modulation of cytokine function by heparan sulfate proteoglycans : sophisticated models for the regulation of cellular responses to cytokines." Proc.Assoc.Am.Physicians. 110. 118-125 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tsukada, Junichi: "Human T-cell leukemia virus type I tax transactivates the promortor of human prointerleukin-1beta gene through association with two transcription factors, nuclear factor-interleukin-6 and Spi-1." Blood. 90. 3142-3153 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Isida, Osamu: "Chondrocyte are regulated by cellular adhesion through CD44 and hyalronic acid pathway." J.Bone Miner.Res.12. 1657-1663 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mori, Naoki: "Characterization and regulation of interleukin-4 receptor in adult T cell leukemia cells." Eur.J.Haematol.56. 241-247 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Okada,Yousuke: "Short term treatment of recombinant murine interleukin-4 rapidly inhibits bone formation in normal and overiectomized mine." Bone. 22. 361-368 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tanaka,Yoshiya: "Constitutive chemokine production results in activation of leukocyte function-associated antigen-1 on adult T cell lekemia cells." Blood. 91. 3309-3919 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tanaka,Yoshiya: "Modulation of cytokine function by heparan sulfate proteoglycans:sophisticated models for regulation of cellular responses to cytokines." Proc.Assoc.Am.Physicians. 110. 118-125 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tsukada,Junichi: "Human T-cell leukemia virus type I tax transactivates the promortor of human prointerleukin-β gene through association with two transcription factors,nuclear factor-interleukin-6 and Spi-1." Blood. 90. 3142-3153 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Isida,Osamu: "Chondrocyte are regulated by cellular adhesion through CD44 and hyalronic acid pathway." J.Bone Miner.Res.12. 1657-1663 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Mori,Naoki: "Characterization and regulation of interleukin-4 receptor in adult T cell leukemia cells." Eur.J.Haematol.56. 241-247 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tanaka,Y., Eto,S. 他: "Constitutive chemokine production results in activation of LFA-1 on adult T cell leukemia cells." Blood. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tanaka,Y., Eto,S. 他: "Modulation of cytokine function by heparan sulfate proteoglycans:sophisticated models for the regulation of cellular responses to cytokines." Proc.Assoc.Am.physicians. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tsukada,J., Eto,S. 他: "HTLV-I Tax transactivates the promotor of human pro-IL-Iβ gene through association with two transcription factors,NF-IL6 and Spi-1" Blood. 90・8. 3142-3153 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tanaka,Y., Eto,S. 他: "Distinctive phenotype of leukemic T cells with various tissue tropism" J.Immunology. 158・8. 3822-3829 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tanaka,Y., Eto,S. 他: "Heparan sulfate proteoglycan on leukemic cells is primarily involved in integrin-triggering and its mediated adhesion to endotherial cells." J.Exp.Med.184・11. 1987-1997 (1997)

    • Related Report
      1997 Annual Research Report

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

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