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2002 Fiscal Year Final Research Report Summary

Clinical application of limitin that has anti-tumor and anti-viral activity

Research Project

Project/Area Number 13557081
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Hematology
Research InstitutionOsaka University

Principal Investigator

ORITANI Kenji  Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (70324762)

Co-Investigator(Kenkyū-buntansha) KADOYA Toshihiko  Kirin Brewery Co. LTD., Pharmaceutical Research Laboratory, Chief, 医薬探索研究所, 主任研究員
TOMIYAMA Yoshiaki  Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (80252667)
Project Period (FY) 2001 – 2002
KeywordsInterferon / Limitin / anti-tumor / immunoregulatory / anti-viral / myelosuppression / gene expression / signals
Research Abstract

Limitin is an interferon (IFN)-like cytokine that has sequence homology with previously known type I IFNs and utilizes the IFN-α/β receptor for its biological activities. Using our established the anti-limitin antibody and recombinant limitin protein, we compared biological functions between limitin and IFN-α, and analyzed in vivo expression of limitin protein. (1) Limitin augmented the killer activity of cytotoxic T lymphocytes as well as the surface expression of MHC class I molecules. Limitin inhibited the proliferation of FDCP-1 cells stably transfected with p210bcr/abl. Limitin also induced antiviral state against EMCV, MHV, and HSV. Although the above functions of limitin were similar to those of IFN-α, higher concentration of limitin was required than IFN-α for the inhibition of CFU-IL7 or CFU-Meg colony formation. Limitin could not inhibit CFU-GM or BFU-E colony formation while IFN-α did. These data suggest that limitin may be less toxic than other IFNs, and therefore may have a unique
clinical niche for treatment of diseases where type I IFNs have proven useful. (2) Immunohistochemical analysis revealed that the limitin protein is produced by mature T lymphocytes in spleen and thymus in healthy mice. This result propose that cDNA from human thymus is a suitable source of cDNA library to screen human homolog of limitin. (3) The disruption of tyrosine kinase Tyk2 completely abrogated IFN-α-induced inhibition of CFU-IL7 and CFU-Meg colony formation as well as up-regulation and translocation of DAXX. These data indicate that Tyk2 plays an important role in IFN-mediated myelosuppression, and we are now analyzing the difference of signaling pathways between limitin and IFN-α.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Oritani K: "Type I interferons and limitin : a comparison of structures, receptors, and functions"Cytokine Growth Factor Rev. 12. 337-348 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Oritani K: "Limitin : an interferon-like cytokine without myeloerythroid suppressive properties"J Mol Med. 79. 168-174 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takahashi I: "A new IFN-like cytokine, limitin, modulates the immune response without influencing thymocyte development"J Immunol. 167. 3156-3163 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kouro T: "Characteristics of early murine B-lymphocyte precursors and their direct sensitivity to negative regulators"Blood. 97. 2708-2715 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shimoda K: "Cutting edge : tyk2 is required for the induction and nuclear translocation of Daxx which regulates IFN-alpha-induced suppression of B lymphocyte formation"J Immunol. 169. 4707-4711 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Oritani K: "T lymphocytes constitutively produce an interferonlike cytokine limitin characterized as a heat-and acid-stable and heparin-binding glycoprotein"Blood. 101. 178-185 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Oritani K, et al: "Type I interferons and limitin: a comparison of structures, receptors, and functions."Cytokine Growth Factor Rev.. 12. 337-348 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Oritani K, et al: "Limitin: an interferon-like cytokine without myelo-erythroid suppressive properties."J Mol Med. 79. 168-74 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi I, et al: "A new interferon like cytokine, limitin modulates the immune response without influencing thymocyte-development."J Immunol. 167. 3156-3163 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kouro T, et al: "Characteristics of early murine B-lyraphocyte precursors and their direct sensitivity to negative regulators"Blood. 97. 2708-2715

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shimoda K, et al: "Cutting edge: tyk2 is required for the induction and nuclear translocation of Daxx which regulates IFN-alpha-induced suppression of B lymphocyte formation."J Immunol. 169. 4707-4711 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Oritani K, et al: "T lymphocytes constitutively : produce an interferonlike cytokine limitin characterized as a heat- and acid-stable and heparin-binding glycoprotein."Blood. 101. 178-185 (2003)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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