ESE-1 Is a Novel Transcriptional Mediator of Inflammation That Interacts with NF-κB to Regulate the Inducible Nitric-oxide Synthase Gene

• Published in: The Journal of biological chemistry Vol. 276; no. 5; p. 3302
• Main Authors: Susan Rudders, John Gaspar, Rebecca Madore, Carole Voland, Franck Grall, Anand Patel, Andrea Pellacani, Mark A. Perrella, Towia A. Libermann, Peter Oettgen
• Format: Journal Article
• Language: English
• Published: American Society for Biochemistry and Molecular Biology 02.02.2001
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M006507200

Inflammation is a hallmark of several vascular diseases. The nuclear factor κB (NF-κB) 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-κB 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-κB, and cotransfection of ESE-1 with the p50 and p65 subunits of NF-κB 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.