Progesterone is essential for protecting against LPS-induced pregnancy loss. LIF as a potential mediator of the anti-inflammatory effect of progesterone.
Progesterone is essential for protecting against LPS-induced pregnancy loss. LIF as a potential mediator of the anti-inflammatory effect of progesterone.
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DOI：
10.1371/journal.pone.0056161
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Franchi AM
中科院分区：
文献类型：
--
作者：
Aisemberg J;Vercelli CA;Bariani MV;Billi SC;Wolfson ML;Franchi AM
在妊娠第7天给予小鼠脂多糖（LPS），24 h后胚胎吸收率为100%。在这个模型中，一氧化氮是吸收过程的基础。预后可能是负责的，至少部分地，在胎儿-母体界面的Th 2开关，诱导对胎儿抗原的主动免疫耐受。Th 2细胞促进T细胞的发育，产生白血病抑制因子（LIF），由于其在妊娠早期的免疫调节作用，LIF似乎很重要。我们的目的是评估孕酮参与LPS诱导的胚胎吸收机制，以及LIF是否可以介导激素作用。使用体内和体外模型，我们提供的证据表明，循环孕酮是一个重要组成部分的过程中，感染导致胚胎吸收小鼠。此外，LIF似乎是炎症条件下孕酮效应的介导者。我们发现，血清孕酮下降到非常低的水平后，24小时的LPS暴露。此外，孕激素补充防止胚胎吸收和LPS诱导的子宫一氧化氮水平在体内的增加。结果显示，LPS在处理6和12小时后减少了子宫中核孕酮受体的表达。我们研究了LIF在妊娠小鼠子宫组织中的表达，发现孕酮在体外上调LIF mRNA的表达。我们观察到LIF能够调节LPS体外诱导的一氧化氮水平，这表明它可能是孕酮炎症作用的潜在介质。我们的观察结果支持这样一种观点，即孕酮作为抗炎剂在成功妊娠中起着关键作用，并且它可能在预防与炎症性疾病相关的早期生殖衰竭方面具有可能的治疗应用。
Lipopolysaccharide (LPS) administration to mice on day 7 of gestation led to 100% embryonic resorption after 24 h. In this model, nitric oxide is fundamental for the resorption process. Progesterone may be responsible, at least in part, for a Th2 switch in the feto-maternal interface, inducing active immune tolerance against fetal antigens. Th2 cells promote the development of T cells, producing leukemia inhibitory factor (LIF), which seems to be important due to its immunomodulatory action during early pregnancy. Our aim was to evaluate the involvement of progesterone in the mechanism of LPS-induced embryonic resorption, and whether LIF can mediate hormonal action. Using in vivo and in vitro models, we provide evidence that circulating progesterone is an important component of the process by which infection causes embryonic resorption in mice. Also, LIF seems to be a mediator of the progesterone effect under inflammatory conditions. We found that serum progesterone fell to very low levels after 24 h of LPS exposure. Moreover, progesterone supplementation prevented embryonic resorption and LPS-induced increase of uterine nitric oxide levels in vivo. Results show that LPS diminished the expression of the nuclear progesterone receptor in the uterus after 6 and 12 h of treatment. We investigated the expression of LIF in uterine tissue from pregnant mice and found that progesterone up-regulates LIF mRNA expression in vitro. We observed that LIF was able to modulate the levels of nitric oxide induced by LPS in vitro, suggesting that it could be a potential mediator of the inflammatory action of progesterone. Our observations support the view that progesterone plays a critical role in a successful pregnancy as an anti-inflammatory agent, and that it could have possible therapeutic applications in the prevention of early reproductive failure associated with inflammatory disorders.
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