Estrogen receptor α antagonists mediate changes in CCL20 and CXCL1 secretions in the murine female reproductive tract.
Estrogen receptor α antagonists mediate changes in CCL20 and CXCL1 secretions in the murine female reproductive tract.
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DOI：
10.1111/aji.12021
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发表时间：
2013-02
期刊：
影响因子：
--
通讯作者：
Wira CR
中科院分区：
文献类型：
--
作者：
Hickey DK;Fahey JV;Wira CR
雌二醇调节子宫上皮细胞的趋化因子分泌，但对体内雌二醇的调节或雌激素受体（er）的作用知之甚少。用选择性雌激素受体调节剂（SERMs）处理BALB/c小鼠后，将其生殖液中CCL20和CXCL1的含量与雌二醇处理后的小鼠发情期和发情期进行比较。使用离体阴道和子宫上皮/基质细胞确定细胞调控。子宫/阴道趋化因子分泌受周期性调节，高雌二醇时CCL20最低，CXCL1最高，一般模拟体内雌二醇的作用。体外子宫上皮细胞分泌CCL20/CXCL1和体内阴道分泌CCL20均受ERα调控，而不受ERβ调控。雌二醇/SERMs不能改变去卵巢小鼠子宫CCL20分泌。卵巢切除术后子宫上皮ERα染色降低与子宫组织雌二醇无反应性相对应。ERα调节雌性生殖道CCL20/CXCL1的分泌，ERα拮抗剂直接对抗雌二醇的调节。了解内质网介导的抗菌趋化因子表达对于阐明对性传播病原体的循环易感性具有重要意义。
Estradiol regulates chemokine secretion from uterine epithelial cells but little is known about estradiol regulation in vivo or the role of estrogen receptors (ERs). CCL20 and CXCL1, present in reproductive washes following treatment with selective estrogen receptor modulators (SERMs) were compared with that during estrous, and following estradiol treated ovariectomized BALB/c mice. Cellular regulation was determined using isolated vaginal and uterine epithelial/stromal cells in vitro. Uterine/vaginal chemokine secretion is cyclically regulated with CCL20 lowest but CXCL1 highest during high estradiol, generally mimicking estradiol effect in vivo. ERα but not ERβ regulated CCL20/CXCL1 secretion by uterine epithelial cells in vitro and vaginal CCL20 in vivo. Estradiol/SERMs failed to alter uterine CCL20 secretion in ovariectomized mice. Diminished uterine epithelial ERα staining following ovariectomy corresponded with estradiol unresponsiveness of uterine tissue. ERα regulates CCL20/CXCL1 secretion in the female reproductive tract and ERα antagonists directly oppose the regulation by estradiol. Understanding ER mediated antimicrobial chemokine expression is important to elucidate cyclic susceptibility to sexually transmitted pathogens.
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