Kappa B-type enhancers are involved in lipopolysaccharide-mediated transcriptional activation of the tumor necrosis factor alpha gene in primary macrophages.

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Serval ID
serval:BIB_18187BA8802F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Kappa B-type enhancers are involved in lipopolysaccharide-mediated transcriptional activation of the tumor necrosis factor alpha gene in primary macrophages.
Journal
The Journal of experimental medicine
Author(s)
Shakhov A.N., Collart M.A., Vassalli P., Nedospasov S.A., Jongeneel C.V.
ISSN
0022-1007
ISSN-L
0022-1007
Publication state
Published
Issued date
01/01/1990
Peer-reviewed
Oui
Volume
171
Number
1
Pages
35-47
Language
english
Notes
Publication types: Comparative Study ; Journal Article
Publication Status: ppublish
Abstract
We have explored the cis-acting elements necessary for the LPS-mediated activation of the mouse TNF-alpha promoter by transfecting a set of 5' deletion mutants linked to the CAT reporter gene into primary bone marrow-derived macrophages. A major drop in inducibility by LPS was seen upon deletion of a region mapping between nt -655 and nt -451. Gel retardation assays revealed that LPS induced the appearance in this region of several specific DNA-protein complexes mapping to sequence motifs with strong homology to the kappa B enhancer. Constructs containing two or more copies of one of the kappa B enhancer motifs linked to a heterologous promoter were inducible by LPS. Additional deletion of a region between nt -301 and nt -241, which contains a MHC class II-like "Y box" and formed a Y box-specific complex with a protein whose concentration was increased by LPS, caused a nearly complete loss of inducibility by LPS. We speculate that NF-kappa B and/or related proteins are involved in the LPS-induced transcriptional activation of the TNF-alpha gene, and that factors interacting with the Y box can additionally modulate the activity of the gene in macrophages.
Keywords
Animals, B-Lymphocytes/immunology, Base Sequence, Cells, Cultured, Enhancer Elements, Genetic, Gene Expression Regulation, Genes/drug effects, Genes, Immunoglobulin, Humans, Immunoglobulin kappa-Chains/genetics, Lipopolysaccharides/pharmacology, Macrophages/drug effects, Macrophages/immunology, Mice, Mice, Inbred C57BL, Molecular Sequence Data, Oligonucleotide Probes, Plasmids, Promoter Regions, Genetic, Restriction Mapping, Sequence Homology, Nucleic Acid, Transcription, Genetic/drug effects, Tumor Necrosis Factor-alpha/genetics
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 15:39
Last modification date
09/08/2024 14:52
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