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The C/EBP bZIP domain can mediate lipopolysaccharide induction of the proinflammatory cytokines interleukin-6 and monocyte chemoattractant protein-1.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2000 May 26; Vol. 275 (21), pp. 16373-81. - Publication Year :
- 2000
-
Abstract
- C/EBPalpha, beta, and delta are all expressed by bone marrow-derived macrophages. Ectopic expression of any of these transcription factors is sufficient to confer lipopolysaccharide (LPS)-inducible expression of interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) to a B lymphoblast cell line, which normally lacks C/EBP factors and does not display LPS induction of proinflammatory cytokines. Thus, the activities of C/EBPalpha, beta, and delta are redundant in regard to expression of IL-6 and MCP-1. Surprisingly, the bZIP region of C/EBPbeta, which lacks any previously described activation domains, can also confer LPS-inducible expression of IL-6 and MCP-1 in stable transfectants. Transient transfections reveal that the bZIP regions of C/EBPbeta, C/EBPdelta, and, to a lesser extent, C/EBPalpha can activate the IL-6 promoter and augment its induction by LPS. Furthermore, the transdominant inhibitor, LIP, can activate expression from the IL-6 promoter. The ability of the C/EBPbeta bZIP region to activate the IL-6 promoter in transient transfections is completely dependent upon an intact NF-kappaB-binding site, supporting a model where the bZIP protein primarily functions to augment the activity of NF-kappaB. Replacement of the leucine zipper of C/EBPbeta with that of GCN4 yields a chimeric protein that can dimerize and specifically bind to a C/EBP consensus sequence, but shows a markedly reduced ability to activate IL-6 and MCP-1 expression. These results implicate the leucine zipper domain in some function other than dimerization with known C/EBP family members, and suggest that C/EBP redundancy in regulating cytokine expression may result from their highly related bZIP regions.
- Subjects :
- Animals
B-Lymphocytes
Binding Sites
CCAAT-Enhancer-Binding Protein-beta
CCAAT-Enhancer-Binding Proteins
Cell Line
Chemokine CCL2 genetics
DNA-Binding Proteins genetics
Dimerization
Fungal Proteins genetics
Gene Expression Regulation
Interleukin-6 genetics
Mice
NF-kappa B metabolism
Nuclear Proteins analysis
Nuclear Proteins genetics
Promoter Regions, Genetic
Protein Isoforms metabolism
Protein Kinases genetics
Recombinant Fusion Proteins genetics
Repressor Proteins pharmacology
Transcription Factors genetics
Transcriptional Activation
Transfection
Chemokine CCL2 biosynthesis
DNA-Binding Proteins metabolism
Interleukin-6 biosynthesis
Leucine Zippers genetics
Lipopolysaccharides pharmacology
Nuclear Proteins metabolism
Saccharomyces cerevisiae Proteins
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 275
- Issue :
- 21
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 10748205
- Full Text :
- https://doi.org/10.1074/jbc.M910269199