EFFECTS OF GLUCOCORTICOIDS ON THE TPA-INDUCED MONOCYTIC DIFFERENTIATION
EFFECTS OF GLUCOCORTICOIDS ON THE TPA-INDUCED MONOCYTIC DIFFERENTIATION
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DOI：
10.1002/jlb.52.2.173
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发表时间：
1992-08-01
影响因子：
5.5
通讯作者：
GOPPELTSTRUEBE, M
中科院分区：
文献类型：
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作者：
HOFF, T;SPENCKER, T;GOPPELTSTRUEBE, M
以人单核细胞U937为模型系统，研究糖皮质激素对单核细胞分化的影响。与5 × 10(-9) M的12- o -十四烷醇-13-乙酸磷酯（TPA）孵育48 - 72小时后，未成熟的U937细胞停止增殖，在形态和功能上变成巨噬细胞样。用糖皮质激素（地塞米松和强的松，10（-7）和10(-6)M）而不是黄体酮（10(-6)M）对细胞进行预孵育，效果显著：细胞保持悬浮状态，细胞间相互作用很少。荧光活化细胞分选分析表明，这与表面分子ICAM-1和CD18的表达减少有关。tpa诱导的细胞释放溶菌酶或产生活性氧自由基的能力（以硝基蓝四氮唑的还原来确定）明显降低。环加氧酶活性的诱导，从而释放前列腺素的能力几乎完全被消除。当TPA后24或48小时给予糖皮质激素时，也观察到前列腺素合成的抑制。然而，通过活性测量和Western blot分析发现，TPA诱导的第一步，蛋白激酶C的激活和易位不受糖皮质激素的影响。随后tpa诱导的c-fos诱导没有变化。在糖皮质激素存在或不存在的情况下，用TPA处理的细胞中，分化相关癌基因c-myc和c-myb的下调是相同的。此外，糖皮质激素对tpa诱导的生长停滞没有显著影响。因此，糖皮质激素干扰tpa诱导的功能，这是活化巨噬细胞的典型特征；然而，它们不损害分化过程和伴随的生长抑制。
The human monocytic cell line U937 was used as a model system to investigate the effects of glucocorticoids on monocytic differentiation. Upon incubation with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) (5 x 10(-9) M) for 48 to 72 h, the immature U937 cells ceased to proliferate and became morphologically and functionally macrophage-like. Preincubation of the cells with glucocorticoids (dexamethasone and prednisolone, 10(-7) and 10(-6) M) but not progesterone (10(-6) M) had marked effects: The cells remained in suspension and developed very little cell-cell interaction. This correlated with decreased expression of the surface molecules ICAM-1 and CD18 as determined by fluorescence-activated cell sorter analysis. The TPA-induced ability of the cells to release lysozyme or to generate reactive oxygen radicals (determined as reduction of nitroblue tetrazolium) was markedly reduced. The induction of cyclooxygenase activity and thus the ability to release prostanoids was almost completely abolished. Inhibition of prostanoid synthesis was also observed when the glucocorticoids were administered 24 or 48 h after TPA. The primary step of TPA induction, the activation and translocation of protein kinase C, however, was not affected by glucocorticoids as determined by activity measurements and Western blot analysis. There was no change in the subsequent TPA-induced induction of c-fos. The down-regulation of the differentiation-related oncogenes c-myc and c-myb was the same in cells treated with TPA in the presence or absence of glucocorticoids. Furthermore, no significant effect of glucocorticoids on the TPA-induced growth arrest was observed. Glucocorticoids thus interfere with TPA-induced functions, which are typical for activated macrophages; however, they do not impair the differentiation process and concomitant growth inhibition.