title: Role of CAAT-enhancer binding protein isoforms in the cytokine regulation of acute-phase plasma protein genes.
abstract: Rat hepatic cells respond to interleukin (IL) -1, IL-6, and dexamethasone treatment by increasing the transcription rate of acute-phase plasma protein genes. The same conditions lead to changes in the expression of CAAT-enhancer binding protein (C/EBP) isoforms which are specific to the hepatic cell line. To identify the relationship between C/EBP isoforms and acute-phase protein gene activation, the hormone-specific expression of C/EBP alpha, beta, and delta was determined in H-35 and HTC cells and was compared to acute-phase liver. C/EBP beta was found to be the principal isoform in hepatoma cells and to be strongly stimulated by cytokines and dexamethasone in H-35 cells. Transactivating functions were observed for all three C/EBP isoforms by cotransfection of CAT gene reporter constructs containing cytokine and glucocorticoid response elements of acute-phase protein genes and expression plasmids for mouse C/EBP alpha, beta, and delta into rat and human hepatoma cells. The degree of C/EBP-mediated transactivation was, however, extremely variable among the different regulatory elements. Transcription run-on reactions with nuclei from transiently transfected H-35 cells indicated that cotransfected C/EBP beta increases basal expression of reporter gene constructs as well as the dexamethasone-mediated stimulation of constructs containing the glucocorticoid response elements of the rat alpha 1-acid glycoprotein gene, but did not accelerate or enhance hormone-dependent transcription activation of reporter gene plasmids containing the IL-6 regulatory element of the beta-fibrinogen gene. Activation of the reporter gene constructs appeared to be temporally and quantitatively correlated with the amount of nuclear C/EBP as determined by two-dimensional Western and Southwestern blot analyses.
authors.affiliation: Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York 14263.
authors.forename: H
authors.initials: H
authors.lastname: Baumann
authors.forename: K K
authors.initials: KK
authors.lastname: Morella
authors.forename: S P
authors.initials: SP
authors.lastname: Campos
authors.forename: Z
authors.initials: Z
authors.lastname: Cao
authors.forename: G P
authors.initials: GP
authors.lastname: Jahreis
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics*; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D002451:Cell Compartmentation / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000145:classification / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000502:physiology*; D051379:Mice; D009687:Nuclear Proteins / Q000145:classification / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D014157:Transcription Factors / Q000145:classification / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D000209:Acute-Phase Proteins; D022762:CCAAT-Enhancer-Binding Proteins; D016207:Cytokines; D004268:DNA-Binding Proteins; D006728:Hormones; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors