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

UNIL restricted access
State: Public
Version: Final published version
License: Not specified
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
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
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