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Title

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

Authors
Shakhov, A N
Nedospasov, S A
Jongeneel, C V
Published in Journal of Experimental Medicine. 1990, vol. 171, no. 1, p. 35-47
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 AnimalsB-Lymphocytes/immunologyBase SequenceCells, CulturedEnhancer Elements, GeneticGene Expression RegulationGenes/drug effectsGenes, ImmunoglobulinHumansImmunoglobulin kappa-Chains/geneticsLipopolysaccharides/pharmacologyMacrophages/drug effects/immunologyMiceMice, Inbred C57BLMolecular Sequence DataOligonucleotide ProbesPlasmidsPromoter Regions, GeneticRestriction MappingSequence Homology, Nucleic AcidTranscription, Genetic/drug effectsTumor Necrosis Factor-alpha/genetics
Identifiers
PMID: 2104921
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Research group Groupe Collart Martine (microbiologie et médecine moléculaire) (81)
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SHAKHOV, A N et al. Kappa B-type enhancers are involved in lipopolysaccharide-mediated transcriptional activation of the tumor necrosis factor alpha gene in primary macrophages. In: Journal of Experimental Medicine, 1990, vol. 171, n° 1, p. 35-47. https://archive-ouverte.unige.ch/unige:30052

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