| Project/Area Number |
07670387
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | The Kitasata Institute |
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Principal Investigator |
KATAGIRI Takuya The Kitasato Institute, Center for Basic Research Project Leader, 基礎研究所, 室長 (70126100)
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| Co-Investigator(Kenkyū-buntansha) |
OUMI Shinobu Institute of Medical Science, The University of Tokyo, Associate Professor, 医科学研究所, 助教授 (20160046)
KAKINUMA Shizuko The Kitasato Institute, Center for Basic Research, Researcher, 基礎研究所, 研究員
MATSUI Hidenori The Kitasato Institute, Center for Basic Research, Project Leader, 基礎研究所, 室長補佐 (30219373)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1995: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Immunity / differentiation / protein-tyrosine kinase / apoptosis / Fyn / MRL / Mp-Ipr / Ipr mouse / HL-60 / retinoic acid |
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| Research Abstract |
1.We prepared and analyzed MRL / Mp-lpr / Ipr (MRL / Ipr) mice lacking tyrosine kinase Fyn to understand the role of Fyn in the development of autoimmune disease. The results showed that life span of these mice was elongated twice as long as that of intact MRL / Ipr mince. Development of both the immune-complex glomerulonephritis and the massive lymphadenopathy was suppressed in the Fyn-deficient MRL / lpr mice. Among IgG subtypes, IgG3 type of anti-DNA autoantibody were specifically diminished in these mutant mice. Taken together, we conclude that Fyn is involved in the growth of autoreactive T cells in the periphery and the production of IgG3 type of anti-DNA antibody in the autoimmune mice. We propose that Fyn may become a target molecule for treatment of patients with SLE-like autoimmune disease.
We found that an inhibitor for protein-tyrosine kinase in combination with retionoic acid (RA) causes apoptosis of human promyelocytic leukemia cell, HL-60. We detected marked tyrosine-phosphorylation of tyrosine kinases, Lyn and Fgr accompanying granulocytic differentiation of RA-stimulated HL-60 cells. Analyzes using antisense oligonucleotides specific for Lyn or Fgr, demonstrate that these these kinases funcition as anti-apoptotic mokecules to promote granulocytic differentiation of HL-60 cells.From these results, we propose that tyrosine kinases such as Lyn or Fgr may become a target for apotosis-inducing treatment of promyelocytic leukemia.
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