Interaction of cytokine- and glucocorticoid-response elements of acute-phase plasma protein genes. Importance of glucocorticoid receptor level and cell type for regulation of the elements from rat alpha 1-acid glycoprotein and beta-fibrinogen genes.
Dexamethasone increased the transscriptional activity of several acute-phase plasma protein genes in cytokine-treated HepG2 cells, suggesting the presence of functional glucocorticoid receptors (GR). The level of GR was, however, insufficient for stimulation of transiently transfected gene constructs containing glucocorticoid-response elements (GRE). By complementation of HepG2 cells with a GR expression vector, a cell system was generated that allowed analysis of the interaction between GRE and cytokine-response elements of the rat alpha 1-acid glycoprotein gene and identification of the principal regulatory elements of the rat beta-fibrinogen gene. Although the expression of plasmid-derived GR mRNA was reduced by dexamethasone treatment, the concentration of GR was sufficient for full, short-term stimulation of GRE-containing vectors. By comparing the pattern of regulation of the cloned GRES in HepG2 and mouse L-cells, an equivalent, cell-type independent dexamethasone response was monitored for the alpha 1-acid glycoprotein element but a response limited to HepG2 cells was found for the beta-fibrinogen element. The data indicate that, although substantial differences exist in the organization and composition of the regulatory elements of the two genes, the overall function is, nevertheless, remarkably similar.
Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York 14263.
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D000209:Acute-Phase Proteins / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D005340:Fibrinogen / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D005796:Genes / Q000187:drug effects; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D007700:Kinetics; D008969:Molecular Sequence Data; D009961:Orosomucoid / Q000235:genetics*; D010957:Plasmids; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012045:Regulatory Sequences, Nucleic Acid; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection
D000209:Acute-Phase Proteins; D007377:Interleukin-3; D015850:Interleukin-6; D009961:Orosomucoid; D011965:Receptors, Glucocorticoid; D011994:Recombinant Proteins; D003907:Dexamethasone; D005340:Fibrinogen