Ray P, Ghosh S K, Zhang D H, Ray A
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
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.
细胞因子白细胞介素-6（IL-6）是肝脏免疫和急性期反应的关键介质，也与子宫功能有关。雌激素是子宫基质细胞产生IL-6的有效抑制剂。在子宫内膜腺癌细胞系Ishikawa中，佛波酯诱导的IL-6启动子激活以野生型受体依赖的方式被17β-雌二醇（E2）抑制至基础水平。虽然他莫昔芬已被证明对子宫内膜有雌激素作用，但它并不抑制IL-6启动子的诱导。我们之前表明，E2对IL-6基因表达的抑制不涉及雌激素受体（ER）与IL-6 DNA的高亲和力结合。我们现在报告，ER可直接与转录因子NF-IL6和NF-κB相互作用，并可抑制它们结合DNA的能力，这可能是雌激素抑制IL-6基因表达的分子基础。
