ESE-1 is a novel transcriptional mediator of inflammation that interacts with NF-kappa B to regulate the inducible nitric-oxide synthase gene

J Biol Chem. 2001 Feb 2;276(5):3302-9. doi: 10.1074/jbc.M006507200. Epub 2000 Oct 17.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding Sites
  • Calcium-Binding Proteins*
  • Cells, Cultured
  • Cytokines / pharmacology
  • DNA-Binding Proteins*
  • Humans
  • Inflammation / metabolism
  • Inflammation Mediators / metabolism
  • Inflammation Mediators / physiology
  • Membrane Glycoproteins / metabolism
  • Mutation
  • NF-kappa B / metabolism*
  • NF-kappa B / physiology
  • Nerve Tissue Proteins / metabolism
  • Nitric Oxide Synthase / metabolism*
  • Nitric Oxide Synthase Type II
  • Promoter Regions, Genetic / drug effects
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins c-ets
  • Proto-Oncogene Proteins*
  • Synaptotagmin I
  • Synaptotagmins
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Trans-Activators / physiology*
  • Transcription Factors*
  • Transcriptional Activation
  • Vascular Diseases / metabolism


  • Calcium-Binding Proteins
  • Cytokines
  • DNA-Binding Proteins
  • ELF3 protein, human
  • Inflammation Mediators
  • Membrane Glycoproteins
  • NF-kappa B
  • Nerve Tissue Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ets
  • Synaptotagmin I
  • Trans-Activators
  • Transcription Factors
  • Synaptotagmins
  • NOS2 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II