Phorbol Ester-Induced Reversible Inactivation of Cytotoxic T Cell Function: Correlation with Down-Regulation of Protein Kinase C Activity.
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概要
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When an H-2<SUP>d</SUP>-specific cytotoxic T lymphocytes (CTL) clone, FC1, was incubated in the presence of 10<SUP>-7</SUP> M phorbol myristate acetate (PMA) for 10-12 hr, the cytolytic activity of the CTL against H-2<SUP>d</SUP> target cells was abrogated, but was reversibly restored to the normal level after subsequent incubation of the cells in PMA-free medium for more than 10 hr. These effects of PMA have been reported (Russell, J.H.: J. Immunol. 133, 907-912 (1984)), but the mode of its action has not been fully investigated. Here, we analyzed the biochemical basis of the PMA-induced loss of cytolytic activity. Cycloheximide completely blocked the restoration of the PMA-suppressed cytolytic activity, suggesting that protein synthesis was required in this process. PMA-treatment did not affect the levels of CD3 and CD8 molecules expressed on the CTL, nor was the level of a CTL-specific serine esterase, BLT esterase, affected by this treatment. However, the target cell-induced release of BLT esterase from the CTL was suppressed if the cells were pretreated with PMA. PMA-treatment of the CTL led to the down-regulation of protein kinase C (PKC) activity by about 50%. On the other hand, staurosporin, an inhibitor of PKC, completely blocked the target cell lysis when added at 10<SUP>-6</SUP> M. These results suggest that the down-regulation of at least some isoform(s) of PKC is responsible for the PMA-induced loss of the cytotolytic activity of CTL.
- 公益社団法人 日本薬理学会の論文
著者
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Ohmori Hitoshi
Department Of Bioscience And Biotechnology Graduate School Of Natural Science And Technology Okayama
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Hikida Masaki
Department Of Biotechnology Faculty Of Engineering Okayama University
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Takai Toshiyuki
Department Of Biotechnology Faculty Of Engineering Okayama University
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Ohmori Hitoshi
Department of Biotechnology, Faculty of Engineering, Okayama University
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TAKAI Toshiyuki
Department of Biotechnology, Faculty of Engineering, Okayama University
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Shimada Toshitaka
Department of Biotechnology, Faculty of Engineering, Okayama University
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