Cooperative interaction of NF-kappaB and C/EBP binding sites is necessary for manganese superoxide dismutase gene transcription mediated by lipopolysaccharide and interferon-gamma

FEBS Lett. 1999 Apr 23;449(2-3):115-9. doi: 10.1016/s0014-5793(99)00408-1.


Expression of the manganese superoxide dismutase (Mn-SOD) is induced by pro-inflammatory cytokines. We investigated the cis-acting elements within a tumor necrosis factor-responsive element (TNFRE) which was identified in the second intron of the murine Mn-SOD gene. Site-directed mutagenesis, reporter plasmid transfection studies and electrophoretic mobility shift assays demonstrated that inducible transcription factors enhanced the transcriptional activity of the Mn-SOD gene through the TNFRE. The cooperation between proteins binding to the newly identified NF-kappaB and C/EBP sites led to synergistic gene transcription. This report provides the first evidence that cooperation between two distinct cis-acting elements may be required for induction of Mn-SOD gene expression mediated by lipopolysaccharide and interferon-gamma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Binding Sites
  • CCAAT-Enhancer-Binding Proteins
  • DNA-Binding Proteins / metabolism*
  • Enhancer Elements, Genetic
  • Gene Expression Regulation, Enzymologic*
  • Interferon-gamma / metabolism*
  • Interferon-gamma / pharmacology
  • Lipopolysaccharides / metabolism*
  • Lipopolysaccharides / pharmacology
  • Manganese
  • Mice
  • NF-kappa B / metabolism*
  • NF-kappa B p50 Subunit
  • Nuclear Proteins / metabolism*
  • Rats
  • Recombinant Proteins
  • Superoxide Dismutase / genetics*
  • Transcription Factor RelA
  • Transcription, Genetic


  • CCAAT-Enhancer-Binding Proteins
  • DNA-Binding Proteins
  • Lipopolysaccharides
  • NF-kappa B
  • NF-kappa B p50 Subunit
  • Nuclear Proteins
  • Recombinant Proteins
  • Transcription Factor RelA
  • Manganese
  • Interferon-gamma
  • Superoxide Dismutase