Domin W S, Chait A, Deeb S S
Department of Medicine, University of Washington, Seattle 98195.
Biochemistry. 1991 Mar 12;30(10):2570-4. doi: 10.1021/bi00224a002.
The effect of dexamethasone on lipoprotein lipase (LPL) gene expression during macrophage differentiation was investigated by using the human monocytic leukemia cell line THP-1 and human monocyte-derived macrophages. Addition of dexamethasone to THP-1 cells increased steady-state levels of LPL mRNA and LPL mass accumulation in the medium during PMA-induced differentiation by 4-fold. Studies with human monocyte-derived macrophages showed a similar effect of dexamethasone on LPL expression. Peak LPL mRNA levels were achieved 24-h post-dexamethasone addition to THP-1 cells. Optimal stimulation of LPL mRNA occurred when dexamethasone was added 24 h after induction with PMA. Thereafter, there was rapid decline in responsiveness to dexamethasone. Induction of LPL mRNA in THP-1 cells was completely blocked by actinomycin D, suggesting that induction was transcription dependent. The stability of LPL mRNA was not influenced by dexamethasone. Treatment of THP-1 cells with PMA led to a 2-fold increase in specific binding of dexamethasone and a 4-fold increase in glucocorticoid receptor mRNA within 12 h. Thus, dexamethasone stimulates LPL gene expression during differentiation of human macrophages, a process that involves induction of glucocorticoid receptor synthesis and activation.
利用人单核细胞白血病细胞系THP-1和人单核细胞衍生的巨噬细胞，研究了地塞米松在巨噬细胞分化过程中对脂蛋白脂肪酶（LPL）基因表达的影响。在PMA诱导的THP-1细胞分化过程中，添加地塞米松可使培养基中LPL mRNA的稳态水平和LPL质量积累增加4倍。对人单核细胞衍生的巨噬细胞的研究表明，地塞米松对LPL表达有类似的作用。在向THP-1细胞添加地塞米松后24小时达到LPL mRNA水平峰值。当在PMA诱导后24小时添加地塞米松时，LPL mRNA受到最佳刺激。此后，对地塞米松的反应迅速下降。放线菌素D完全阻断了THP-1细胞中LPL mRNA的诱导，表明诱导是转录依赖性的。地塞米松不影响LPL mRNA的稳定性。用PMA处理THP-1细胞导致地塞米松特异性结合增加2倍，糖皮质激素受体mRNA在12小时内增加4倍。因此地塞米松在人巨噬细胞分化过程中刺激LPL基因表达，这一过程涉及糖皮质激素受体合成和激活的诱导。
