Can medroxyprogesterone acetate alter Toll-like receptor expression in a mouse model of intrauterine inflammation?
Can medroxyprogesterone acetate alter Toll-like receptor expression in a mouse model of intrauterine inflammation?
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DOI：
10.1016/j.ajog.2005.05.043
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发表时间：
2005-09-01
影响因子：
9.8
通讯作者：
Mrinalini, C
中科院分区：
文献类型：
--
作者：
Elovitz, MA;Mrinalini, C
目的：先天免疫受体toll样受体2和toll样受体4的激活对于宿主对革兰氏阳性和革兰氏阴性生物的炎症反应至关重要。这些受体可以启动和调节炎症反应。toll样受体的差异调节可能是宫内炎症信号分娩的机制之一。同样，孕激素可能有能力改变这种影响。这些研究是为了阐明子宫内炎症和醋酸甲孕酮对子宫内炎症小鼠模型中子宫、子宫颈和胎盘中toll样受体表达的影响。研究设计：在妊娠第15天，CD-1小鼠随机分为醋酸甲孕酮或对照体预处理组，然后宫内输注脂多糖或无菌生理盐水。宫内输注6小时后，取出子宫、宫颈和胎盘组织。提取RNA和蛋白质。对toll样受体2和4信使RNA进行定量聚合酶链反应。使用toll样受体4特异性抗体进行Western blot分析。结果：宫内炎症可上调子宫、子宫颈和胎盘中toll样受体2和4信使RNA。醋酸甲孕酮预处理可降低脂多糖诱导的宫颈和胎盘toll样受体2和4信使RNA的上调。在脂多糖存在的情况下，醋酸甲孕酮不能阻止脂多糖诱导的子宫toll样受体4信使RNA和蛋白的增加。妊娠小鼠单独使用醋酸甲孕酮可显著增加子宫中toll样受体4信使RNA的表达。结论：宫内炎症对toll样受体2和toll样受体4的表达有差异影响。子宫中toll样受体2在宫内脂多糖作用下的上调可能是炎症反应增强的一种机制，可能有助于促进炎症环境下的分娩。因此，醋酸甲孕酮抑制脂多糖诱导的toll样受体2信使RNA上调的能力可能是孕激素能够减少早产的机制之一。(C) 2005 Mosby, Inc。版权所有。
Objective: Activation of the innate immune receptors, Toll-like receptors 2 and 4, are critical for a host inflammatory response to both Gram-positive and Gram-negative organisms. These receptors can initiate and modulate the inflammatory response. Differential regulation of Toll-like receptors may be one of the mechanisms by which intrauterine inflammation signals parturition. Likewise, progestational agents may have the ability to modify this effect. These studies were performed to elucidate the effect of intrauterine inflammation and medroxyprogesterone acetate on Toll-like receptor expression in the uterus, cervix, and placenta in a mouse model of intrauterine inflammation.Study design: On day 15 of gestation, CD-1 mice were randomized to pretreatment with medroxyprogesterone acetate or vehicle before intrauterine infusion with lipopolysaccharide or sterile saline solution. Six hours after intrauterine infusion, uterine, cervical, and placental tissues were harvested. RNA and protein were extracted. Quantitative polymerase chain reaction was performed for Toll-like receptor 2 and 4 messenger RNA. Western blot analysis was performed with Toll-like receptor 4-specific antibodies.Results: Intrauterine inflammation up-regulated Toll-like receptor 2 and 4 messenger RNA in uterus, cervix, and placenta. Pretreatment with medroxyprogesterone acetate decreased the lipopolysaccharide-induced up-regulation of Toll-like receptor 2 and 4 messenger RNA in the cervix and placenta. Medroxyprogesterone acetate treatment, in the presence of lipopolysaccharide, was unable to prevent the lipopolysaccharide-induced increase in Toll-like receptor 4 messenger RNA and protein in the uterus. Medroxyprogesterone acetate treatment alone in pregnant mice significantly increased Toll-like receptor 4 messenger RNA expression in the uterus.Conclusion: Intrauterine inflammation has a differential effect on Toll-like receptor 2 and 4 expression. The observed up-regulation of Toll-like receptor 2 in the uterus in response to intrauterine lipopolysaccharide may be a mechanism to augment the inflammatory response and may serve to promote parturition in the setting of inflammation. Consequently, the ability of medroxyprogesterone acetate to suppress lipopolysaccharide-induced up-regulation of Toll-like receptor 2 messenger RNA may be one of the mechanisms by which progestins are able to decrease preterm birth. (C) 2005 Mosby, Inc. All rights reserved.