DIFFERENTIAL REGULATION OF MACROPHAGE CCAAT-ENHANCER BINDING PROTEIN ISOFORMS BY LIPOPOLYSACCHARIDE AND CYTOKINES

The regulation of the C/EBP family in macrophages by LPS and cytokines is of potentially crucial importance in several pathophysiological conditions. The action of LPS and three cytokines on the expression of C/EBP mRNA, protein and functional DNA binding activity in the murine J774.2 cell line was...

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Bibliographic Details
Published in:Cytokine (Philadelphia, Pa.) Pa.), 2000-09, Vol.12 (9), p.1430-1436
Main Authors: Tengku-Muhammad, Tengku S, Hughes, Timothy R, Ranki, Harri, Cryer, Anthony, Ramji, Dipak P
Format: Article
Language:English
Subjects:
Animals
Blotting, Western
CCAAT-enhancer binding protein/cytokines/J774.2 cell line/lipopolysaccharide/gene expression
CCAAT-Enhancer-Binding Proteins - chemistry
CCAAT-Enhancer-Binding Proteins - metabolism
Cell Line
Cell Nucleus - metabolism
Cytokines - metabolism
DNA - metabolism
Interferon-gamma - pharmacology
Interleukin-1 - pharmacology
Kinetics
Lipopolysaccharides - metabolism
Macrophages - metabolism
Mice
Protein Binding
Protein Isoforms
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - metabolism
Time Factors
Tumor Necrosis Factor-alpha - pharmacology
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Summary:The regulation of the C/EBP family in macrophages by LPS and cytokines is of potentially crucial importance in several pathophysiological conditions. The action of LPS and three cytokines on the expression of C/EBP mRNA, protein and functional DNA binding activity in the murine J774.2 cell line was therefore studied. Exposure of the cells to LPS, IL-1, IFN-γ and TNF-α produced a reduction of C/EBPα mRNA levels and a corresponding increase in the expression of C/EBPβ and C/EBPδ. EMSA showed time-dependent changes in the DNA binding activity of individual C/EBP isoforms and demonstrated the participation of heterodimers between the different members in DNA–protein interactions. Additionally, mediator-specific changes in the kinetics and magnitude of C/EBP mRNA expression pattern and profile of DNA-protein interactions were observed. These studies provide novel insights into the potential mechanisms that may be responsible for the mediator-specific regulation of macrophage gene expression through the C/EBP family.
ISSN:1043-4666
1096-0023
DOI:10.1006/cyto.2000.0711