title: Transcriptional activation of the lipoprotein lipase gene in macrophages by dexamethasone.
abstract: 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.
authors.affiliation: Department of Medicine, University of Washington, Seattle 98195.
authors.forename: W S
authors.initials: WS
authors.lastname: Domin
authors.forename: A
authors.initials: A
authors.lastname: Chait
authors.forename: S S
authors.initials: SS
authors.lastname: Deeb
mesh_terms: 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*
chemical_list: D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D003609:Dactinomycin; D003907:Dexamethasone; D008071:Lipoprotein Lipase