Inhibition of proliferation and of IL-2 production and utilization in lymphocytes by S-oxalylglutathione.
Inhibition of proliferation and of IL-2 production and utilization in lymphocytes by S-oxalylglutathione.
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S-草酰谷胱甘肽抑制淋巴细胞的增殖以及 IL-2 的产生和利用。
DOI：
10.1006/excr.1996.0167
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Mastro,AM
中科院分区：
文献类型：
--
作者：
Grove,DS;Crowl,CV;Gagajewski,A;Yang,CS;Reddy,GR;Hamilton,GA;Mastro,AM
以前我们已经表明，S-β-胡萝卜素（草酸的单硫醇酯）是普遍存在的哺乳动物代谢物，其浓度下降时，淋巴细胞被刺激增殖。本研究旨在进一步探讨S-β蛋白在细胞增殖过程中的作用。当加入到伴刀豆球蛋白A刺激的淋巴细胞中时，S-草酰谷胱甘肽（GS-Ox）在约100 μ mol/L时抑制DNA合成50%。0.15在0.5mM时，抑制率几乎为100%。GS-Ox的存在阻断了IL-2的产生，但IL-2的加入不允许DNA合成进行。GS-Ox还抑制IL-2依赖性细胞系BT 2的增殖。在初级淋巴细胞GS-Ox减少IL-2受体的表达，但不是在IL-2依赖性母细胞系。总体RNA合成和蛋白质合成没有显着改变GS-Ox。淋巴细胞与GS-Ox孵育后，阳性转录因子NF-κB的水平降低，但阴性转录因子NREA的量基本不变。这些结果不仅进一步证明了S-β-葡聚糖是小分子细胞增殖抑制剂，而且在一定程度上阐明了S-β-葡聚糖调节活化反应的具体步骤。
Previously we have shown thatS-oxalins (monothiolesters of oxalic acid) are ubiquitous mammalian metabolites whose concentrations decrease when lymphocytes are stimulated to proliferate. The present study was undertaken to further examine the role ofS-oxalins in the proliferation process. When added to lymphocytes stimulated with concanavalin A, theS-oxalin,S-oxalylglutathione (GS-Ox), inhibited DNA synthesis by 50% when present at ca. 0.15 mMand virtually 100% at 0.5 mM.The inhibition was reversible. The presence of GS-Ox blocked IL-2 production, but addition of IL-2 did not permit DNA synthesis to proceed. GS-Ox also inhibited proliferation of an IL-2-dependent cell line, BT2. In primary lymphocytes GS-Ox reduced IL-2 receptor expression, but not in an IL-2-dependent blast cell line. Overall RNA synthesis and protein synthesis were not significantly altered by GS-Ox. Levels of the positive transcription factor, NF-κB, were decreased after incubation of lymphocytes with GS-Ox, but the amount of a negative transcription factor, NREA, was largely unchanged. The results not only provide further evidence thatS-oxalins are small-molecule cell proliferation inhibitors, they also clarify to some extent the specific steps in the activation response modulated byS-oxalins.