Department of Biology, 9201 University City Boulevard, University of North Carolina at Charlotte, Charlotte, NC 28223, United States.
Mol Cell Endocrinol. 2010 Oct 26;328(1-2):87-92. doi: 10.1016/j.mce.2010.07.017. Epub 2010 Jul 21.
Studies to define the effects of estrogens on immune function have yielded conflicting results. The recent demonstration that GPR30 can mediate rapid non-genomic events and may function as a novel transmembrane estrogen receptor could provide a mechanism underlying such findings. In this study, we have investigated the ability of GPR30 to regulate cell-surface expression of Toll-like receptor 4 (TLR4), a key molecule in the perception of bacterial lipopolysaccharide (LPS) by immune cells. We show that 17beta-estradiol or GPR30-specific agonists decrease TLR4 expression on macrophages within 10-60 min and such effects were abolished following GPR30 knockdown. Importantly, GPR30 ligation significantly reduces sensitivity of these immune cells to LPS challenge as determined by reductions in inflammatory mediator production. Based on these findings, we suggest that estrogen may utilize this non-classical estrogen receptor to limit potentially lethal acute inflammatory responses without compromising long-term host defense.
研究雌激素对免疫功能的影响产生了相互矛盾的结果。最近的研究表明，GPR30 可以介导快速的非基因组事件，并可能作为一种新型的跨膜雌激素受体发挥作用，这为这些发现提供了一种机制。在这项研究中，我们研究了 GPR30 调节细胞表面 Toll 样受体 4（TLR4）表达的能力，TLR4 是免疫细胞感知细菌脂多糖（LPS）的关键分子。我们发现，17β-雌二醇或 GPR30 特异性激动剂在 10-60 分钟内降低巨噬细胞表面 TLR4 的表达，并且这种作用在 GPR30 敲低后被消除。重要的是，GPR30 配体的结合显著降低了这些免疫细胞对 LPS 挑战的敏感性，这可以通过减少炎症介质的产生来确定。基于这些发现，我们认为雌激素可能利用这种非经典的雌激素受体来限制潜在的致命性急性炎症反应，而不损害长期宿主防御。
