Identification of pathway-selective estrogen receptor ligands that inhibit NF-κ3 transcriptional activity
Identification of pathway-selective estrogen receptor ligands that inhibit NF-κ3 transcriptional activity
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DOI：
10.1073/pnas.0405841102
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发表时间：
2005-02-15
影响因子：
11.1
通讯作者：
Harnish, DC
中科院分区：
文献类型：
--
作者：
Chadwick, CC;Chippari, S;Harnish, DC
炎症现在被认为是许多疾病如动脉粥样硬化、类风湿性关节炎和炎症性肠病的关键组成部分。转录因子NF-κ B已被证明参与炎症增殖过程的早期和晚期阶段。在这份报告中，我们描述了识别的途径选择性雌激素受体（ER）配体，WAY-169916，抑制NF-κ B转录活性，但没有传统的雌激素活性。这种途径选择性配体不促进雌激素的经典作用，如刺激子宫增殖或ER介导的基因表达，但它是一种有效的抑制剂，如炎症性肠病的HLA-B27转基因大鼠模型所示。我们的研究结果表明，在慢性炎症性疾病的治疗途径选择性ER配体，如WAY-1 69916的潜在效用。
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-kappaB 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-kappaB 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-1 69916 in the treatment of chronic inflammatory diseases.