Transcriptional regulation through cytokine and glucocorticoid response elements of rat acute phase plasma protein genes by C/EBP and JunB.
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.
Baumann
H
H
Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York 14263.
Jahreis
G P
GP
Morella
K K
KK
Won
K A
KA
Pruitt
S C
SC
Jones
V E
VE
Prowse
K R
KR
D000209:Acute-Phase Proteins / Q000235:genetics*; D000818:Animals; D001798:Blood Proteins / Q000235:genetics*; D022762:CCAAT-Enhancer-Binding Proteins; D002461:Cell Line, Transformed; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D003513:Cycloheximide / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism*; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D010957:Plasmids; D051381:Rats; D014157:Transcription Factors; D014158:Transcription, Genetic; D014162:Transfection
D000209:Acute-Phase Proteins; D001798:Blood Proteins; D022762:CCAAT-Enhancer-Binding Proteins; D016207:Cytokines; D004268:DNA-Binding Proteins; D005938:Glucocorticoids; D009687:Nuclear Proteins; D014157:Transcription Factors; D003513:Cycloheximide; D015500:Chloramphenicol O-Acetyltransferase