Auwerx J H, Deeb S, Brunzell J D, Peng R, Chait A
Department of Medicine, University of Washington, Seattle 98195.
Biochemistry. 1988 Apr 19;27(8):2651-5. doi: 10.1021/bi00408a003.
Stimulation of the macrophage-like cell line THP-1 with the phorbol ester phorbol 12-myristate 13-acetate (PMA) resulted in differentiation into cells with many features of macrophages. This differentiation was accompanied by transcriptional activation of the lipoprotein lipase (LPL) and apo E genes and accumulation of their protein products in the media. PMA-induced differentiation of the HEL and HL-60 cell lines was not accompanied by induction of the gene for LPL, whereas the apo E gene was induced slightly in HL-60 cells. By contrast, the gene for superoxide dismutase (SOD-1) was either unaffected (THP-1) or down regulated (HL-60 or HEL cells) by PMA treatment. Induction of LPL mRNA in THP-1 cells was dependent upon the concentration of phorbol ester added. A minimal concentration of 1.6 x 10(-8) M PMA was necessary for macrophage differentiation, induction of LPL mRNA, and synthesis of the enzyme. LPL mRNA accumulates within 3 h after stimulation with PMA and attains a maximum concentration after 6 h, thereafter slowly decreasing over the next 3 days. In contrast, the steady-state level of apo E mRNA in the same THP-1 cultures increased gradually over a period of 48 h after induction. These studies thus demonstrate that THP-1 cells are of value as a model to study the quantitative and temporal expression of the LPL and apo E genes during macrophage differentiation.
用佛波酯佛波醇12 -肉豆蔻酸酯13 -乙酸酯（PMA）刺激巨噬细胞样细胞系THP - 1，可使其分化为具有巨噬细胞多种特征的细胞。这种分化伴随着脂蛋白脂肪酶（LPL）和载脂蛋白E（apo E）基因的转录激活以及它们的蛋白质产物在培养基中的积累。PMA诱导的HEL和HL - 60细胞系分化并未伴随LPL基因的诱导，而apo E基因在HL - 60细胞中略有诱导。相比之下，超氧化物歧化酶（SOD - 1）基因在PMA处理后在THP - 1细胞中未受影响，而在HL - 60或HEL细胞中则被下调。THP - 1细胞中LPL mRNA的诱导取决于所添加佛波酯的浓度。巨噬细胞分化、LPL mRNA的诱导以及该酶的合成所需的PMA最低浓度为1.6×10⁻⁸ M。用PMA刺激后，LPL mRNA在3小时内积累，并在6小时后达到最大浓度，此后在接下来的三天中缓慢下降。相比之下，同一THP - 1培养物中apo E mRNA的稳态水平在诱导后48小时内逐渐升高。因此，这些研究表明，THP - 1细胞作为研究巨噬细胞分化过程中LPL和apo E基因定量和时间表达的模型具有重要价值。
