IL-1β-mediated proinflammatory responses are inhibited by estradiol via down-regulation of IL-1 receptor type I in uterine epithelial cells
IL-1β-mediated proinflammatory responses are inhibited by estradiol via down-regulation of IL-1 receptor type I in uterine epithelial cells
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DOI：
10.4049/jimmunol.175.10.6509
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发表时间：
2005-11-15
影响因子：
4.4
通讯作者：
Wira, CR
中科院分区：
文献类型：
--
作者：
Schaefer, TM;Wright, JA;Wira, CR
本研究的目的是研究性激素对il -10介导的子宫上皮细胞反应的影响。在雌二醇和黄体酮存在的情况下，IL-1 β刺激子宫上皮细胞，检测人β -防御素-2和CXCL8 mRNA的表达和分泌。雌二醇抑制IL-1 β介导的mRNA表达和人β -防御素-2和CXCL8在子宫上皮细胞的分泌，而孕酮则无作用。雌二醇对il -10介导的抑制作用是剂量依赖性的，使用10（-7）到10(-10)M观察到最大的抑制作用，并且被证明是通过雌激素受体介导的，因为添加纯雌激素受体拮抗剂消除了这种作用。雌二醇抑制IL-1 β介导的子宫上皮细胞应答的机制可能是下调IL-1R 1型，从而降低子宫上皮细胞对IL-1 β的应答能力。这些结果表明，雌二醇对il -10介导的子宫上皮细胞炎症反应的抑制作用表明内分泌和免疫系统之间存在联系，可能对抑制排卵或怀孕期间的促炎反应至关重要。
The objective of this study was to examine the effects of sex hormones on IL-10-mediated responses by uterine epithelial cells. The mRNA expression and secretion of human beta-defensin-2 and CXCL8 by uterine epithelial cells was examined following stimulation with IL-1 beta in the presence of estradiol or progesterone. Estradiol inhibited the IL-1 beta-mediated mRNA expression and secretion of human beta-defensin-2 and CXCL8 by uterine epithelial cells while progesterone had no effect. Inhibition of the IL-10-mediated response by estradiol was dose dependent, with maximal inhibition observed using 10(-7) to 10(-10) M, and was shown to be mediated through the estrogen receptor because addition of a pure estrogen receptor antagonist abrogated this effect. The mechanism by which estradiol inhibits IL-1 beta-mediated responses by uterine epithelial cells appears to be the down-modulation of the IL-1R type 1, thereby reducing the uterine epithelial cell's ability to respond to IL-1 beta. These results suggest that the inhibitory effect of estradiol on IL-10-mediated inflammatory responses by uterine epithelial cells indicates a link between the endocrine and immune systems and may be crucial for dampening proinflammatory responses during the time of ovulation or pregnancy.