雌激素受体α介导Toll样受体2激动剂诱导系膜细胞产生单核细胞趋化蛋白-1。
Estrogen receptor-alpha mediates Toll-like receptor-2 agonist-induced monocyte chemoattractant protein-1 production in mesangial cells.
作者信息
Dasgupta Subhajit, Eudaly Jackie
机构信息
(Autoimmunity and Neurodegeneration), Department of Neuroscience, (Neurosciences and Neuroscience research), Medical University of South Carolina, Charleston, SC 29425, USA.
Rheumatology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA.
出版信息
Results Immunol. 2012 Nov 10;2:196-203. doi: 10.1016/j.rinim.2012.10.002. eCollection 2012.
TLR2 agonists are well known for inducing NF-kB activation and inflammation, while estrogen receptor-alpha (ER-α) is a regulator of estrogen-mediated anti-inflammatory responses. In the present work, we determined the role of ER-α and phosphorylated ER-α in TLR2 agonist-induced MCP1 production in mesangial cells. We found that TLR2 agonists induced nuclear localization of phospho-ER-α (serine 118), and estrogen and TLR2 agonists both induced phosphorylation of ER-α at the serine 118 and 104/106 positions. Incubation of MRL/lpr mesangial cells with estrogen was found to attenuate TLR2 agonist-mediated MCP1 production. To determine the mode of action of ER-α/pER-α (serine-118), we used the ER-α inhibitor MPP and transfected mesangial cells with ER-α siRNA. ER-α inhibition was found to decrease MCP1 production in mesangial cells. Thus, ER-α/pER-α is an intermediate regulator for both TLR2-mediated MCP1 production during inflammation and estrogen-mediated anti-inflammatory signals in mesangial cells.
Toll样受体2（TLR2）激动剂因诱导核因子κB（NF-κB）激活和炎症反应而闻名，而雌激素受体α（ER-α）是雌激素介导的抗炎反应的调节因子。在本研究中，我们确定了ER-α和磷酸化ER-α在TLR2激动剂诱导系膜细胞产生单核细胞趋化蛋白1（MCP1）中的作用。我们发现TLR2激动剂诱导磷酸化ER-α（丝氨酸118）的核定位，雌激素和TLR2激动剂均诱导ER-α在丝氨酸118和104/106位点的磷酸化。用雌激素孵育MRL/lpr系膜细胞可减弱TLR2激动剂介导的MCP1产生。为确定ER-α/磷酸化ER-α（丝氨酸118）的作用方式，我们使用了ER-α抑制剂MPP并用ER-α小干扰RNA（siRNA）转染系膜细胞。发现抑制ER-α可降低系膜细胞中MCP1的产生。因此，ER-α/磷酸化ER-α是炎症期间TLR2介导的MCP1产生和系膜细胞中雌激素介导的抗炎信号的中间调节因子。
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