ESE-1 is a novel transcriptional mediator of inflammation that interacts with NF-kappa B to regulate the inducible nitric-oxide synthase gene.
Inflammation is a hallmark of several vascular diseases. The nuclear factor kappaB (NF-kappaB) transcription factors are dimeric proteins involved in the activation of a large number of genes in response to inflammatory stimuli. We report the involvement of a novel member of the ETS transcription factor, ESE-1, in mediating vascular ... inflammation. ESE-1 is induced in response to inflammatory cytokines and lipopolysaccharide in vascular smooth muscle cells, endothelial cells, and cells of the monocyte-macrophage lineage. This induction occurs within hours of stimulation and is mediated by NF-kappaB transactivation of the ESE-1 promoter. We have identified the inducible form of nitric-oxide synthase (NOS2) as a putative target for ESE-1. ESE-1 can bind to the p50 subunit of NF-kappaB, and cotransfection of ESE-1 with the p50 and p65 subunits of NF-kappaB synergistically enhances transactivation of the NOS2 promoter by ESE-1. An ESE-1-binding site within the NOS2 promoter has been identified, the site-directed mutagenesis of which completely abolishes the ability of ESE-1 to transactivate the NOS2 promoter. Finally, in a mouse model of endotoxemia, associated with acute vascular inflammation, ESE-1 is strongly expressed in vascular endothelium and smooth muscle cells. In summary, ESE-1 represents a novel mediator of vascular inflammation.
Mesh Terms:
Binding Sites, Calcium-Binding Proteins, Cells, Cultured, Cytokines, DNA-Binding Proteins, Humans, Inflammation, Inflammation Mediators, Membrane Glycoproteins, Mutation, NF-kappa B, Nerve Tissue Proteins, Nitric Oxide Synthase, Nitric Oxide Synthase Type II, Promoter Regions, Genetic, Protein Structure, Tertiary, Proto-Oncogene Proteins, Synaptotagmin I, Synaptotagmins, Trans-Activators, Transcription Factors, Transcriptional Activation, Vascular Diseases
Binding Sites, Calcium-Binding Proteins, Cells, Cultured, Cytokines, DNA-Binding Proteins, Humans, Inflammation, Inflammation Mediators, Membrane Glycoproteins, Mutation, NF-kappa B, Nerve Tissue Proteins, Nitric Oxide Synthase, Nitric Oxide Synthase Type II, Promoter Regions, Genetic, Protein Structure, Tertiary, Proto-Oncogene Proteins, Synaptotagmin I, Synaptotagmins, Trans-Activators, Transcription Factors, Transcriptional Activation, Vascular Diseases
J. Biol. Chem.
Date: Feb. 02, 2001
PubMed ID: 11036073
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