Studies on the regulation of cholesteryl ester synthesis and mechanism of lipid accumulation in macrophage cells

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Macrophage cells derived from the human monocytic leukemia cell line, THP-1, accumulate esterified cholesterol when cultivated in the presence of acetylated low-density lipoprotein(Ac-LDL) through scavenger receptors (ScR). In the present study, we isolated a subtype of THP-1 cells that failed to accumulate esterified cholesterol when cultivated in the presence of Ac-LDL.The cells had negligible amounts of cell-association and degradation of Ac-LCL compared to the parent THP-1 cell. The subtype THP-1 cells did not express ScR mRNA as well as that of lipoprotein lipase. In contrast, the expression of apolipoprotein E mRNA was greater than that found in parent THP-1 cells. The culture medium of subtype THP-1 cells treated with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) inhibited the uptake of Ac-LDL and the expression of ScR in parent THP-1 cells. After 48 h incubation in the culture medium containing TPA,the culture medium of differentiated subtype THP-1 cells contained 6.9 ng/ml of tr … More ansforming growth factor (TGF)-beta1, while that of parent THP-1 cells secreted below detection level, which was less than 3 ng/ml. This inhibitory effect of the conditioned medium on the expression of ScR in parent THP-1 cells was abolished by pre-treatment of the culture medium with anti-TGF-beta1 antibodies. Parent THP-1 cells expressed as much amount of TGF-beta1 mRNA as sTHP-1 cells after stimulation of differentiation. Although the precursor forms of TGF-beta1 which were synthesized in both parent and subtype THP-1 cells were of similar size and were expressed at similar levels, latent TGF-beta1-binding protein (LTBP), which is necessary for the secretion of TGF-beta1, could only be co-immunoprecititated with anti- TGF-beta1 antibody from subtype THP-1 cells. This suggests that subtype THP-1 cells secrete TGF-beta1 into the medium by forming a functional complex with LTBp. We conclude that subtype THP-1 cells could not take up Ac-LDL because ScR was inhibited (leading a loss of function) caused by the secreted TGF-beta1. Less