Liang C M, Lee N, Cattell D, Liang S M
Division of Blood and Blood Products, Food and Drug Administration, Bethesda, Maryland.
J Biol Chem. 1989 Aug 15;264(23):13519-23.
In this study, we examined whether and how the cellular activity of interleukin-2 (IL-2) is affected by glutathione (GSH), an important tripeptide existing in most cells. Cell culture and thymidine incorporation assay showed that addition of GSH enhanced the effect of IL-2 on the proliferation and thymidine incorporation of IL-2-dependent cytotoxic T-cells such as CTLL-2 and CT-4R. Treatment of the cells with GSH resulted in a 2-fold increase in the amount of IL-2 bound to the cells and a rapid internalization of the bound IL-2. In addition, the degradation of IL-2 in the cells was enhanced by GSH treatment. These effects of GSH were accompanied by an increase in the intracellular GSH level. L-Buthionine-(S,R)-sulfoximine, an inhibitor of de novo GSH synthesis, blunted the increase of intracellular GSH level and modulated the effect of GSH on IL-2 activity. These results suggest that GSH regulates the binding, internalization, degradation, and T-cell proliferative activity of IL-2; alterations of cellular GSH concentration may thus affect the growth and replication of IL-2-sensitive cytotoxic T-cells.
在本研究中，我们检测了白细胞介素-2（IL-2）的细胞活性是否以及如何受到谷胱甘肽（GSH）的影响，谷胱甘肽是大多数细胞中存在的一种重要三肽。细胞培养和胸腺嘧啶核苷掺入试验表明，添加GSH可增强IL-2对IL-2依赖性细胞毒性T细胞（如CTLL-2和CT-4R）增殖和胸腺嘧啶核苷掺入的作用。用GSH处理细胞导致与细胞结合的IL-2量增加2倍，且结合的IL-2迅速内化。此外，GSH处理增强了细胞内IL-2的降解。GSH的这些作用伴随着细胞内GSH水平的升高。L-丁硫氨酸-（S，R）-亚砜亚胺，一种从头合成GSH的抑制剂，减弱了细胞内GSH水平的升高，并调节了GSH对IL-2活性的作用。这些结果表明，GSH调节IL-2的结合、内化、降解和T细胞增殖活性；因此，细胞内GSH浓度的改变可能影响IL-2敏感的细胞毒性T细胞的生长和复制。
