Expression of the apolipoprotein E gene in a human macrophage-like cell line, THP-1.
The human monocyte-like cell line, THP-1, differentiated into macrophage-like cells on the addition of a phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate. During the course of differentiation of THP-1 cells, the level of transcripts of the apolipoprotein E gene increased. Apolipoprotein E mRNA increased by more than a hundred times compared to the level prior to differentiation. The apolipoprotein E mRNA reached the maximal level on day 2 after the addition of the phorbol ester and then gradually decreased. After the level had decreased to half the maximal value on day 4 it remained constant. The time course of apolipoprotein E secretion, which showed a peak on day 2, was parallel to that of apolipoprotein E protein synthesis. Furthermore, the time course of apolipoprotein E protein synthesis showed a similar profile to that of the apolipoprotein E transcript level. This indicates that the induction of apolipoprotein E expression by the phorbol ester is due mainly to the increase in the number of transcripts. The synthesis of apolipoprotein E protein was reduced by about 60% on treatment of the differentiated THP-1 cells with 5 micrograms/ml of lipopolysaccharide. The presence of 5 micrograms/ml of lipopolysaccharide in the medium reduced the level of apolipoprotein E mRNA by about 50%. Thus the reduction in protein synthesis was mainly explained by the decrease in the level of apolipoprotein E transcripts. This reduction in the mRNA level caused by lipopolysaccharide was not mediated by the tumor necrosis factor or interleukin 1, which are known to reduce the transcriptional and post-transcriptional activity of lipoprotein lipase in adipocytes, respectively.
Menju
M
M
Department of Etiology and Pathophysiology, National Cardiovascular Center Research Institute, Osaka.
Tajima
S
S
Yamamoto
A
A
D001057:Apolipoproteins E / Q000235:genetics*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D001057:Apolipoproteins E; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D013755:Tetradecanoylphorbol Acetate