Repression of interleukin-6 gene expression by 17 beta-estradiol: inhibition of the DNA-binding activity of the transcription factors NF-IL6 and NF-kappa B by the estrogen receptor

FEBS Lett. 1997 Jun 2;409(1):79-85. doi: 10.1016/s0014-5793(97)00487-0.


The cytokine interleukin-6 (IL-6), a key mediator of immune and acute phase responses of the liver, has also been implicated in uterine functions. Estrogens are potent repressors of IL-6 production by uterine stromal cells. In the endometrial adenocarcinoma cell line Ishikawa, phorbol ester-induced activation of the IL-6 promoter was inhibited to basal levels by 17 beta-estradiol (E2) in a wild-type receptor-dependent fashion. Although tamoxifen has been shown to have estrogenic effects on the endometrium, it did not inhibit induction of the IL-6 promoter. We previously showed that inhibition of IL-6 gene expression by E2 does not involve high-affinity binding of the estrogen receptor (ER) to IL-6 DNA. We now report that the ER can directly interact with the transcription factors NF-IL6 and NF-kappa B and can inhibit their ability to bind DNA which might be the molecular basis for repression of IL-6 gene expression by estrogens.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma
  • CCAAT-Enhancer-Binding Proteins
  • DNA-Binding Proteins / antagonists & inhibitors*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Drug Combinations
  • Endometrial Neoplasms
  • Estradiol / pharmacology*
  • Female
  • Gene Expression Regulation / drug effects*
  • Humans
  • Interleukin-6 / genetics*
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Nuclear Proteins / antagonists & inhibitors*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Promoter Regions, Genetic / drug effects
  • Receptors, Estrogen / chemistry
  • Receptors, Estrogen / physiology*
  • Structure-Activity Relationship
  • Tamoxifen / pharmacology
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tumor Cells, Cultured


  • CCAAT-Enhancer-Binding Proteins
  • DNA-Binding Proteins
  • Drug Combinations
  • Interleukin-6
  • NF-kappa B
  • Nuclear Proteins
  • Receptors, Estrogen
  • Tamoxifen
  • Estradiol
  • Tetradecanoylphorbol Acetate