Solito E, Raugei G, Melli M, Parente L
Department of Pharmacology, Sclavo Research Centre, Siena, Italy.
FEBS Lett. 1991 Oct 21;291(2):238-44. doi: 10.1016/0014-5793(91)81293-h.
The effect of dexamethasone on mRNA and protein synthesis of lipocortins (LCT) 1, 2 and 5 has been investigated in U-937 cells. A constitutive expression of both mRNAs and proteins was detected in undifferentiated U-937 cells. This constitutive level was increased time- and dose-dependently by incubation with phorbol myristate acetate (PMA). In U-937 cells differentiated by 24 h incubation with 6 ng/ml PMA, dexamethasone (DEX) (1 microM for 16 h) caused an increased synthesis of the mRNA level of LCT-1 and 2, but not of LCT-5, over the level induced by PMA. DEX had no effect in undifferentiated cells. Moreover, DEX stimulated the extracellular release of LCT-1 and 5, but not of LCT-2, and inhibited the release of PGE2 and TXB2 only in the differentiated U-937 cells. These results suggest that the responsiveness of these cells to glucocorticoids is dependent on the phase of cell differentiation. The selective release of lipocortins by differentiated U-937 cells may explain, at least in part, the inhibition by DEX of the prostanoid release.
已在U-937细胞中研究了地塞米松对脂皮质素（LCT）1、2和5的mRNA及蛋白质合成的影响。在未分化的U-937细胞中检测到了mRNA和蛋白质的组成型表达。通过与佛波酯肉豆蔻酸酯乙酸酯（PMA）孵育，这种组成型水平呈时间和剂量依赖性增加。在经6 ng/ml PMA孵育24小时分化的U-937细胞中，地塞米松（DEX）（1 μM，作用16小时）导致LCT-1和2的mRNA水平合成增加，超过PMA诱导的水平，但LCT-5的mRNA水平未增加。DEX对未分化细胞无作用。此外，DEX刺激了LCT-1和5的细胞外释放，但未刺激LCT-2的释放，并且仅在分化的U-937细胞中抑制了PGE2和TXB2的释放。这些结果表明，这些细胞对糖皮质激素的反应性取决于细胞分化阶段。分化的U-937细胞对脂皮质素的选择性释放可能至少部分解释了DEX对类前列腺素释放的抑制作用。
