Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University of Chicago, Maywood, IL 60153, USA.
Cell Immunol. 2012 Jan-Feb;275(1-2):80-9. doi: 10.1016/j.cellimm.2012.02.014. Epub 2012 Mar 21.
Physical and psychological stressors reduce natural killer cell function. This reduction in cellular function results from stress-induced release of glucocorticoids. Glucocorticoids act upon natural killer cells to deacetylate and transrepress immune response genes through epigenetic processes. However, other than the glucocorticoid receptor, the proteins that participate in this process are not well described in natural killer cells. The purpose of this study was to identify the proteins associated with the glucocorticoid receptor that are likely epigenetic participants in this process. Treatment of natural killer cells with the synthetic glucocorticoid, dexamethasone, produced a significant time dependent reduction in natural killer cell activity as early as 8h post treatment. This reduction in natural killer cell activity was preceded by nuclear localization of the glucocorticoid receptor with histone deacetylase 1 and the corepressor, SMRT. Other class I histone deacetylases were not associated with the glucocorticoid receptor nor was the corepressor NCoR. These results demonstrate histone deacetylase 1 and SMRT to associate with the ligand activated glucocorticoid receptor within the nuclei of natural killer cells and to be the likely participants in the histone deacetylation and transrepression that accompanies glucocorticoid mediated reductions in natural killer cell function.
生理和心理压力会降低自然杀伤细胞的功能。这种细胞功能的降低是由于应激诱导的糖皮质激素释放所致。糖皮质激素作用于自然杀伤细胞，通过表观遗传过程使免疫反应基因去乙酰化和反式沉默。然而，除了糖皮质激素受体之外，参与这个过程的蛋白质在自然杀伤细胞中描述得还不够清楚。本研究的目的是鉴定与糖皮质激素受体相关的蛋白质，这些蛋白质可能是这个过程中的表观遗传参与者。用合成糖皮质激素地塞米松处理自然杀伤细胞，在处理后 8 小时就会导致自然杀伤细胞活性明显的时间依赖性降低。这种自然杀伤细胞活性的降低先于糖皮质激素受体与组蛋白去乙酰化酶 1 和共抑制因子 SMRT 的核定位。其他 I 类组蛋白去乙酰化酶与糖皮质激素受体没有关联，也没有共抑制因子 NCoR。这些结果表明组蛋白去乙酰化酶 1 和 SMRT 与自然杀伤细胞核内配体激活的糖皮质激素受体结合，并可能参与伴随糖皮质激素介导的自然杀伤细胞功能降低的组蛋白去乙酰化和反式沉默。
