C/EBP homologous protein (CHOP) up-regulates IL-6 transcription by trapping negative regulating NF-IL6 isoform

FEBS Lett. 2003 Apr 24;541(1-3):33-9. doi: 10.1016/s0014-5793(03)00283-7.


Interleukin-6 (IL-6) production is up-regulated by several stimuli through the activation of transcription factors. We have previously demonstrated that CCAAT/enhancer binding protein homologous protein (CHOP) positively regulates IL-6 production at the transcriptional level in the human melanoma cell line A375. In this study, we provide evidence that CHOP up-regulates the IL-6 transcription without binding to the IL-6 promoter. CHOP dimerized more preferentially with an inhibitory isoform of nuclear factor for IL-6 expression (LIP (liver-enriched inhibitory protein)) than with a positively acting isoform (LAP, liver-enriched activator protein). These results indicate that CHOP plays an important role in IL-6 production without binding to its promoter, probably by trapping protein(s) such as LIP, which would otherwise inhibit IL-6 transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CCAAT-Enhancer-Binding Protein-beta / metabolism*
  • CCAAT-Enhancer-Binding Proteins / metabolism
  • CCAAT-Enhancer-Binding Proteins / physiology*
  • Cell Line
  • Humans
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / genetics*
  • Models, Biological
  • Promoter Regions, Genetic
  • Protein Isoforms / metabolism
  • Response Elements
  • Transcription Factor CHOP
  • Transcription Factors / metabolism
  • Transcription Factors / physiology*
  • Transcriptional Activation*
  • Tumor Cells, Cultured
  • Up-Regulation


  • CCAAT-Enhancer-Binding Protein-beta
  • CCAAT-Enhancer-Binding Proteins
  • DDIT3 protein, human
  • Interleukin-6
  • Protein Isoforms
  • Transcription Factors
  • Transcription Factor CHOP