ESE-1 is a novel transcriptional mediator of inflammation that interacts with NF-kappa B to regulate the inducible nitric-oxide synthase gene
| Autor: | Rebecca Madore, Susan A. Rudders, Mark A. Perrella, Carole Voland, Franck Grall, Towia A. Libermann, Anand Patel, Andrea Pellacani, Peter Oettgen, John Antonydas Gaspar |
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| Rok vydání: | 2000 |
| Předmět: |
Transcriptional Activation
Vascular smooth muscle Nitric Oxide Synthase Type II Inflammation Nerve Tissue Proteins Biology Biochemistry Proinflammatory cytokine Transactivation chemistry.chemical_compound Synaptotagmins Mediator Proto-Oncogene Proteins medicine Humans Vascular Diseases Promoter Regions Genetic Molecular Biology Transcription factor Cells Cultured Binding Sites Membrane Glycoproteins Proto-Oncogene Proteins c-ets ETS transcription factor family Calcium-Binding Proteins NF-kappa B NF-κB Cell Biology Molecular biology Protein Structure Tertiary DNA-Binding Proteins chemistry Synaptotagmin I Mutation Trans-Activators Cytokines medicine.symptom Inflammation Mediators Nitric Oxide Synthase Transcription Factors |
| Zdroj: | The Journal of biological chemistry. 276(5) |
| ISSN: | 0021-9258 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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