Positive and negative regulatory elements contribute to CpG oligonucleotide-mediated regulation of human IL-6 gene expression

Eur J Immunol. 2000 Jan;30(1):108-16. doi: 10.1002/1521-4141(200001)30:1<108::AID-IMMU108>3.0.CO;2-4.


Oligonucleotides (ODN) expressing immunostimulatory "CpG motifs" activate human RPMI 8226 myeloma cells to secrete IL-6. Using deletion and site-directed mutagenesis of the human (h)IL-6 promoter region, two positive regulatory elements (the binding sites for the 5'-CCAAT / enhancer binding protein-beta and NF-kappaB) were identified. Two negative regulatory elements, the 3'-retinoblastoma control element (RCE) and the binding site for Epstein-Barr virus C-promoter binding factor 1 (CBF1), also contributed to CpG ODN induction of hIL-6 gene expression. Of interest, CpG ODN treatment induced the dissociation of a repressor protein from its 3'-RCE binding site. Thus, CpG ODN regulation of hIL-6 gene expression involves both enhancer and derepression mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CCAAT-Enhancer-Binding Proteins
  • DNA / metabolism
  • DNA-Binding Proteins / metabolism
  • Dinucleoside Phosphates / pharmacology*
  • Gene Expression Regulation*
  • Humans
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / genetics*
  • NF-kappa B / metabolism
  • Nuclear Proteins / metabolism
  • Oligonucleotides / pharmacology*
  • Promoter Regions, Genetic
  • Tumor Cells, Cultured


  • CCAAT-Enhancer-Binding Proteins
  • DNA-Binding Proteins
  • Dinucleoside Phosphates
  • Interleukin-6
  • NF-kappa B
  • Nuclear Proteins
  • Oligonucleotides
  • cytidylyl-3'-5'-guanosine
  • DNA