Tumor necrosis factor alpha induces the expression of the nuclear protein p8 via a novel NF kappaB binding site within the promoter

Horm Metab Res. 2006 Sep;38(9):570-4. doi: 10.1055/s-2006-950503.

Abstract

p8 is a widely expressed HMG-I/Y-like transcription factor which is involved in regulating cell proliferation and tissue stress. Several studies describe a strong upregulation of p8 expression during inflammatory processes like pancreatitis and LPS-induced sepsis. Here we demonstrate that TNFalpha, which is an important inducer of innate defence against gram-negative bacteria, significantly stimulates p8 protein production in H4IIE rat hepatoma cells within 2 hours. Since a putative NF kappaB motif has been described, we further tested whether TNFalpha stimulates p8 expression via activation of NF kappaB. We characterized the TNFalpha-induced binding of NF kappaB to this motif. We show that the TNFalpha-induced NF kappaB pathway contributes to the induction of p8 during pancreatitis and LPS-induced inflammation.

MeSH terms

  • Animals
  • Binding Sites
  • Cell Line, Tumor
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Electrophoretic Mobility Shift Assay
  • Mice
  • NF-kappa B / metabolism*
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Promoter Regions, Genetic*
  • Protein Binding / drug effects
  • Rats
  • Sequence Deletion
  • Time Factors
  • Tumor Necrosis Factor-alpha / pharmacology*

Substances

  • DNA-Binding Proteins
  • NF-kappa B
  • Neoplasm Proteins
  • Nupr1 protein, mouse
  • Tumor Necrosis Factor-alpha