Transcriptional activation of the lipoprotein lipase gene in macrophages by dexamethasone.
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.
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Department of Medicine, University of Washington, Seattle 98195.
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D015152:Blotting, Northern; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004790:Enzyme Induction; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008071:Lipoprotein Lipase / Q000096:biosynthesis / Q000235:genetics*; D008264:Macrophages / Q000201:enzymology*; D012333:RNA, Messenger / Q000032:analysis; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects*
D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D003609:Dactinomycin; D003907:Dexamethasone; D008071:Lipoprotein Lipase