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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Identification of pathway-selective estrogen receptor ligands that inhibit NF-κB transcriptional activity
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Identification of pathway-selective estrogen receptor ligands that inhibit NF-κB transcriptional activity

机译：鉴定抑制NF-κB转录活性的途径选择性雌激素受体配体

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摘要

Inflammation is now recognized as a key component in a number of diseases such as atherosclerosis, rheumatoid arthritis, and inflammatory bowel disease. The transcription factor NF-kB has been shown to be involved in both the early and late stages of the inflammatory-proliferative process. In this report, we describe the identification of the pathway-selective estrogen receptor (ER) ligand, WAY-169916, that inhibits NF-kB transcriptional activity but is devoid of conventional estrogenic activity. This pathway-selective ligand does not promote the classic actions of estrogens such as stimulation of uterine proliferation or ER-mediated gene expression, but is a potent antiinflammatory agent, as demonstrated in the HLA-B27 transgenic rat model of inflammatory bowel disease. Our results indicate the potential utility of pathway-selective ER ligands such as WAY-169916 in the treatment of chronic inflammatory diseases.
机译：现在，炎症被认为是许多疾病的关键成分，例如动脉粥样硬化，类风湿性关节炎和炎症性肠病。转录因子NF-kB已被证明参与炎性增殖过程的早期和晚期。在此报告中，我们描述了途径选择性雌激素受体（ER）配体WAY-169916的鉴定，该配体抑制NF-kB转录活性但缺乏常规的雌激素活性。该途径选择性配体不促进雌激素的经典作用，例如刺激子宫增生或ER介导的基因表达，而是一种有效的抗炎药，如HLA-B27转基因大鼠炎症性肠病模型所证明。我们的结果表明，选择性途径的ER配体（如WAY-169916）在治疗慢性炎性疾病中的潜在用途。

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