A Nuclear Factor for IL-6 Expression (NF-IL6) Is a Member of a C/EBP Family

EMBO J. 1990 Jun;9(6):1897-906.

Abstract

NF-IL6 is a nuclear factor that specifically binds to an IL1-responsive element in the IL-6 gene. In this study the gene encoding NF-IL6 has been cloned by direct screening of a lambda gt11 library using NF-IL6 binding sequence as a ligand. The full-length cDNA encoded a 345 amino acid protein with a potential leucine zipper structure and revealed a high degree of homology to a liver-specific transcriptional factor, C/EBP, at the C-terminal portion. The bacterial fusion protein bound to the CCAAT homology as well as the viral enhancer core sequences as in the case of C/EBP. Recombinant NF-IL6 activated the human IL-6 promoter in a sequence-specific manner. Southern blot analysis demonstrated the high-degree conservation of the NF-IL6 gene through evolution and the existence of several other related genes sharing the DNA-binding domain. NF-IL6 mRNA was normally not expressed, but induced by the stimulation with either LPS, IL-1 or IL-6. Interestingly, NF-IL6 was shown to bind to the regulatory regions for various acute-phase protein genes and several other cytokine genes such as TNF, IL-8 and G-CSF, implying that NF-IL6 has a role in regulation not only for the IL-6 gene but also for several other genes involved in acute-phase reaction, inflammation and hemopoiesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Reaction / genetics
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • CCAAT-Enhancer-Binding Proteins
  • Chemotactic Factors / pharmacology
  • DNA / genetics
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics*
  • Humans
  • Interleukin-1 / pharmacology
  • Interleukin-6 / genetics*
  • Interleukin-8
  • Interleukins / pharmacology
  • Liver / drug effects
  • Liver / metabolism*
  • Molecular Sequence Data
  • Nuclear Proteins / biosynthesis
  • Nuclear Proteins / genetics*
  • Protein Processing, Post-Translational
  • Rats
  • Sequence Homology, Nucleic Acid
  • Transcription Factors / genetics*
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • CCAAT-Enhancer-Binding Proteins
  • Chemotactic Factors
  • DNA-Binding Proteins
  • Interleukin-1
  • Interleukin-6
  • Interleukin-8
  • Interleukins
  • Nuclear Proteins
  • Transcription Factors
  • Tumor Necrosis Factor-alpha
  • DNA

Associated data

  • GENBANK/X52560