Transcriptional activation of the lipoprotein lipase and apolipoprotein E genes accompanies differentiation in some human macrophage-like cell lines

Abstract

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.