Cytokine-inducible expression in endothelial cells of an I kappa B alpha-like gene is regulated by NF kappa B

EMBO J. 1993 Jul;12(7):2773-9.

Abstract

The transient expression of many different genes is mediated by the inducible transcription factor p50-p65 NF kappa B, which in turn is regulated by complex formation with its inhibitor I kappa B alpha. We describe here that in porcine aortic endothelial cells, either IL-1 alpha, TNF alpha or LPS upregulates an inhibitor of NF kappa B which we refer to as ECI-6. ECI-6 is by structural and functional criteria an I kappa B alpha protein, the porcine homologue of MAD-3, pp40 and RL/IF-1. We have studied the promoter of the ECI-6/I kappa B alpha gene and provide three lines of evidence that its expression is directly regulated by NF kappa B. First, the 5' regulatory region of ECI-6/I kappa B alpha contains two sites that bind NF kappa B in electrophoretic mobility shift assays. Second, expression following transfection of an ECI-6/I kappa B alpha promoter-luciferase reporter construct is dependent on a co-transfected NF kappa B-p65 subunit. Third, pretreatment of endothelial cells with antioxidants, agents that inhibit activation of NF kappa B, inhibit the expression of ECI-6/I kappa B alpha. We conclude that the regulated expression of ECI-6/I kappa B alpha could represent a novel feedback mechanism by which NF kappa B downregulates its own activity after transient activation of target genes has been achieved.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding Sites
  • Cells, Cultured
  • Cloning, Molecular
  • Cytokines / physiology*
  • DNA
  • DNA-Binding Proteins / genetics*
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism*
  • Gene Expression Regulation*
  • Molecular Sequence Data
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / genetics*
  • NF-kappa B / physiology*
  • Promoter Regions, Genetic
  • RNA, Messenger / metabolism
  • Sequence Homology, Amino Acid
  • Swine
  • Transcription Factor RelA

Substances

  • Cytokines
  • DNA-Binding Proteins
  • ECI-6 protein, Sus scrofa
  • NF-kappa B
  • RNA, Messenger
  • Transcription Factor RelA
  • DNA

Associated data

  • GENBANK/Z21968