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.
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.
Ray
P
P
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Ghosh
S K
SK
Zhang
D H
DH
Ray
A
A
D000230:Adenocarcinoma; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D004338:Drug Combinations; D016889:Endometrial Neoplasms; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011960:Receptors, Estrogen / Q000737:chemistry / Q000502:physiology*; D013329:Structure-Activity Relationship; D013629:Tamoxifen / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D004338:Drug Combinations; D015850:Interleukin-6; D016328:NF-kappa B; D009687:Nuclear Proteins; D011960:Receptors, Estrogen; D013629:Tamoxifen; D004958:Estradiol; D013755:Tetradecanoylphorbol Acetate