Auwerx J, Staels B, Van Vaeck F, Ceuppens J L
Department of Developmental Biology, Faculty of Medicine, Katholieke Universiteit, Leuven, Belgium.
Leuk Res. 1992;16(3):317-27. doi: 10.1016/0145-2126(92)90070-n.
We studied changes in the three types of Fc gamma receptor (FcR) on the THP-1 human monocytic leukemia cells, after incubation with the phorbol ester, PMA, which has been shown to alter the expression of several genes in these cells. THP-1 cells constitutively express FcRI and FcRII, and PMA down-regulated the expression of both FcRI and FcRII. The FcRIII expression was not detected on either untreated or PMA-treated cells. Addition of PMA to THP-1 cells also resulted in a dose-dependent decrease of CD4 expression, as well as in an increased expression of activation-associated antigens. PMA treatment was followed by a progressive decrease in the steady state level of FcRI mRNA, while FcRII mRNA levels did not change, pointing to different regulatory mechanisms at the pre- and post-transcriptional level respectively. The FcRIII mRNA was undetectable. In order to further delineate the mechanism by which PMA induces alterations in FcR expression, we treated cells with stimulators of protein kinase C, of Ca2+ calmodulin-dependent kinase, and of protein kinase A. Since stimulation of none of these second messenger systems induced similar alterations in FcR expression as PMA we next tested the effects of PMA on differentiation and arrest of proliferation. The changes in FcR only occurred at PMA concentrations capable of inducing cell adherence and an arrest of proliferation, and showed a relatively slow time pattern. This suggested that the alterations in FcR expression may be linked to partial differentiation into a more macrophage-like cell. The changes in FcR expression could furthermore be reproduced by 1,25(OH)2 vitamin D3, another agent capable of differenting monocytes. In conclusion, PMA treatment of THP-1 cells decreases FcRI gene transcription and membrane expression and reduces membrane expression of FcRII. Both changes might be linked with an arrest of cell growth and induction of differentiation.
我们研究了佛波酯PMA孵育THP - 1人单核细胞白血病细胞后，三种类型的Fcγ受体（FcR）的变化，已证明PMA可改变这些细胞中几种基因的表达。THP - 1细胞组成性表达FcRI和FcRII，PMA下调了FcRI和FcRII的表达。在未处理或PMA处理的细胞上均未检测到FcRIII的表达。向THP - 1细胞中添加PMA还导致CD4表达呈剂量依赖性降低，以及活化相关抗原的表达增加。PMA处理后，FcRI mRNA的稳态水平逐渐降低，而FcRII mRNA水平未发生变化，分别表明在转录前和转录后水平存在不同的调节机制。未检测到FcRIII mRNA。为了进一步阐明PMA诱导FcR表达改变的机制，我们用蛋白激酶C、Ca2 + 钙调蛋白依赖性激酶和蛋白激酶A的刺激剂处理细胞。由于这些第二信使系统中的任何一种刺激均未诱导出与PMA相似的FcR表达改变，我们接下来测试了PMA对分化和增殖停滞的影响。FcR的变化仅发生在能够诱导细胞黏附和增殖停滞的PMA浓度下，并且呈现出相对缓慢的时间模式。这表明FcR表达的改变可能与部分分化为更类似巨噬细胞的细胞有关。此外，1,25(OH)2维生素D3（另一种能够使单核细胞分化的试剂）也可重现FcR表达的变化。总之，PMA处理THP - 1细胞可降低FcRI基因转录和膜表达，并降低FcRII的膜表达。这两种变化可能都与细胞生长停滞和分化诱导有关。
