Transcriptional regulation through cytokine and glucocorticoid response elements of rat acute phase plasma protein genes by C/EBP and JunB

• Published in: The Journal of biological chemistry 1991-10, Vol.266 (30), p.20390-20399
• Main Authors: Baumann, H, Jahreis, G P, Morella, K K, Won, K A, Pruitt, S C, Jones, V E, Prowse, K R
• Format: Article
• Language: English
• Subjects: Acute-Phase Proteins - genetics; Animals; Blood Proteins - genetics; CCAAT-Enhancer-Binding Proteins; Cell Line, Transformed; Chloramphenicol O-Acetyltransferase - genetics; Cycloheximide - pharmacology; Cytokines - metabolism; DNA-Binding Proteins; Gene Expression Regulation; Glucocorticoids - metabolism; Nuclear Proteins - metabolism; Plasmids; Rats; Transcription Factors; Transcription, Genetic; Transfection
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)54935-8

Independent of de novo protein synthesis, interleukin-1, interleukin-6, and dexamethasone caused immediate stimulation of transcriptional activity of most major acute phase plasma protein genes in the rat hepatoma H-35 cells. However, activation of alpha 2-macroglobulin and alpha 1-acid glycoprotein genes were delayed by 2-4 h and required ongoing protein synthesis. The hormones also increased transiently the transcription of the junB gene and the amounts of JunB, C/EBP, and C/EBP-like mRNA. To identify whether JunB and C/EBP have the ability to control both the early and late acute phase reactants, expression vectors for mouse C/EBP and JunB together with reporter gene constructs containing recognized hormone-specific regulatory elements were introduced into hepatoma cells. C/EBP displayed prominent transactivation activity with the interleukin-1 and glucocorticoid regulatory elements of alpha 1-acid glycoprotein, the interleukin-1 regulatory element of haptoglobin gene, and the interleukin-6 regulatory element of beta-fibrinogen. The interleukin-6 regulatory elements of the first two genes and the glucocorticoid response element of the third gene were not affected by C/EBP. These data suggest that normal hormone activation of these three acute phase reactant genes might involve, in part, C/EBP-related factors which have a broad range of specificity. H-35 cells stably transformed with a mouse C/EBP expression vector showed an elevated basal level as well as cytokine inducible expression of some but not all acute phase reactants. Cotransfected JunB resulted in reduced activity of cytokine-responsive constructs and in lower transactivation by C/EBP. JunB appears to function as a modulator of plasma protein expression during the course of acute phase response.