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.