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Biological research for elucidation of molecular mechanisms responsible for thymoma-associated myasthenia gravis

Research Project

Project/Area Number 10671259
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Thoracic surgery
Research InstitutionOsaka University

Principal Investigator

MIYOSHI Shinichiro  Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (00190827)

Co-Investigator(Kenkyū-buntansha) OKUMURA Meinoshin  Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (40252647)
YOON Hyung-eun  Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (50283768)
MINAMI Masato  Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (10240847)
TAKEDA Shin-ichi  Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (30236468)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsThymoma / Myasthenia gravis / Interferon-γ / MHC class II / HLA-DR / HLA-DR / インターフェロン・ガンマ / 胸水腫 / MHC class II / CIITA
Research Abstract

Although human thymoma is well-known for its frequent association with autoimmune diseases represented by myasthenia gravis, the pathogenesis of paraneoplastic autoimmune diseases associated with thymoma remains to be elucidated. The aim of this study is to reveal the molecular mechanisms resulting in the thymoma-associated paraneoplastic autoimmune diseases.
Thymic epithelial cells derived from the human normal thymuses or the human thymoma thymomas were cultured in vitro, and the level of MHC molecules induced by Interferon-γ (IFN-γ) was examined by flow cytometric study. Although there was no difference in the expression level of MHC class I molecules on epithelial cells between the normal thymus and the thymomas, MHC class II expression was significantly lower in thymomas than in the normal thymuses. The expression level of MHC class II molecules was shown to be significantly correlated with the proportion of CD3ィイD1+ィエD1 cells in the CD4ィイD1+ィエD1CD8ィイD1-ィエD1 subset in thymoma, suggesting the relation between down-regulation of MHC class II molecules and the impairemnt of T cell development in thymomas.
The molecular mechanism responsible for the impaired expression of IFN-γ dependent MHC class II expression in thymoma was investigated. Gel mobility shift assay was performed to examine the signal transduction from the IFN-γ receptor to the nucleus, and translocation of Stat-1 molecule from the cytoplasm to the nucleus was confirmed in thymomas as well as the normal thymus. Then, the induction of CIITA in response to IFN-γ was evaluated by the method of quantitative RT-PCR. The induction of CIITA was shown to be down-regulated in thymoma epithelial cells compared with that in the normal thymus.
These results seem to indicate the possible role of impaired CIITA expression in the abnormal T cell development in thymomas, which results in the onset of paraneoplastic autoimmune diseases.

Report

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

    (4 results)

All Other

All Publications (4 results)

  • [Publications] M Inoue, Y Fujii, M Okumura, Y Takeuchi, H Shiono, S Miyoshi, H Matsuda, R Shirakura.: "Neoplastic thymic epithelial cells of human thymoma support T cell development from CD4ィイD1-ィエD1 CD8ィイD1-ィエD1 cells to CD4ィイD1+ィエD1 CD8ィイD1+ィエD1 cells in vitro"Clinical and Experimental Immunology. 112. 419-426 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] M Inoue, M Okumura, S Miyoshi, H Shiono, K Fukuhara, Y Kadota, H Matsuda, R Shirakura.: "Imapired expression of MHC class II molecules in response to Interferongamma(IFN-γ) on human thymoma neoplastic epithelial cells."Clinical and Experimental Immunology. 117. 1-7 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] M Inoue, M Okumura, Y Fujii, S Miyoshi, H Shiono, K Fukuhara, Y Kadota, H Matsuda, R Shirakura.: "Immaturity of lymphocytes in the metastatic lesions of thymoma."Clinical immunology and Immunolopathology. 88. 249-255 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Masayoshi Inoue: "Impaired expression of MHC class II molecules in response to Intorferon-gamma on human thymoma neoplastic epithelial cells" clinical and Experimental Immunology. in press.

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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