Regulatory mechanism for the induction and degradation of IL-2 mRNA in stimulated T lymphocytes.
| Project/Area Number |
63570224
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Immunology
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| Research Institution | KUMAMOTO UNIVERSITY |
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Principal Investigator |
ONOUE Kaoru Institute for Medical Immunology, Department of Biochemistry, Kumamoto University Medical School, Professor, 医学部, 教授 (60037497)
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| Co-Investigator(Kenkyū-buntansha) |
OHMURA Takafumi Institute for Medical Immunology, Department of Biochemistry, Kumamoto Universit, 医学部, 助手 (30185384)
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| Project Period (FY) |
1988 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1989: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1988: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | IL-2 mRNA induction / signal transduction / protein kinase C / human T cell stimulation / stability of IL-2 mRNA / regulation of IL-2 production / IL-2産生誘導とプロテインキナ-ゼC / インターロイキン2mRNA / プロモータ結合蛋白 / mRNA分解速度 / リンホカイン産生刺激伝達 |
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| Research Abstract |
The object of this research was to analyze the mechanism regulating the induction and the degradation of the interleukin2(IL-2) mRNA in stimulated human T lymphocytes. Our study indicated that, in the stimulated T cells, not only the production of IL-2 mRNA is induced but also the rate of the degradation of synthesized IL-2 mRNA is significantly reduced and the activation of protein kinase C(PKC) is involved in both of these mechanisms, as summarized below.
1) First we reconfirmed our previous results and others that PKC is necessary to induce IL-2 mRNA production in the stimulated T cells by showing the stimulant-dose-related translocation of PKC from cytosol to membrane fraction and inhibition of IL-2 mRNA production by PKC inhibitors, staurosporin A, H-7 and K252a.
2) The increased IL-2 mRNA level in T cells stimulated with PDB (phorboldibutylester) and a calcium ionophore A23187 dropped rather rapidly when the stimulants were removed and mRNA synthesis was stopped by actinomycin D. The rate of this decrease, however, was found to be reduced when the T cells was restimulated by PDB and A23187. The effect of these stimulants was clearly inhibited by PKC inhibitors, staurosporin A, H-7 or K252a.
3) Among three types of PKC isozymes, type II and III were abundant in Tlymphocytes and we found that these isozymes were down regulated by stimulation of the cells.
4) We confirmed that the rate of the degradation of ^<32>P-IL-2 mRNA, prepared by in vitro transcription of IL-2 cDNA, by the polysomal fraction of PDB-stimulated T cells was reduced as compared with the polysomal fraction of unstimulated T cells. Our study thus demonstrates that the induction of IL-2 production is regulated by the rate of the production of IL-2 mRNA and also by the rate of degradation, and PKC is critically involved in both of these processes.
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Report
(3 results)
Research Products
(1 results)
