Dept. of Physiology, Univ. of Siena, Italy.
Am J Physiol Endocrinol Metab. 2010 Mar;298(3):E411-8. doi: 10.1152/ajpendo.00522.2009.
Successful pregnancy involves a series of events, most of them mediated by hormones and cytokines. Estrogens, besides being important for placental growth and embryo development, have a marked effect on the immune system exerting either pro- or anti-inflammatory properties. Numerous studies suggest that estrogens directly affect cellular function, including cytokine production. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine involved in pregnancy, particularly during the earlier stages of placentation. Since reports on mice have shown that estrogens modulate MIF, herein we investigated the effect of estrogens on human placental MIF. By using an in vitro model of first-trimester chorionic villous explants, we found that 17beta-estradiol (E(2)) was able to modulate the release of MIF in a dose-dependent manner (10(-12) vs. 10(-9) M, P < 0.05; 10(-9) vs. 10(-5) M, P < 0.05; 10(-12) vs. 10(-5) M, P < 0.001). Unlike MIF release, no significant change in tissue MIF protein or MIF mRNA was observed. We showed evidence that E(2) concentrations (10(-9) and 10(-5) M) act on placental tissue downregulating the mRNA and protein expression of the ATP-binding cassette transporter protein A1, a membrane transporter involved in MIF secretion. These findings emphasize the mutual cooperation between hormones and cytokines and suggest that increasing estrogen levels with advancing gestation may have a major role in regulating placental MIF secretion.
成功的妊娠涉及一系列事件，其中大多数由激素和细胞因子介导。雌激素除了对胎盘生长和胚胎发育很重要外，还对免疫系统具有明显的影响，表现出抗炎或促炎特性。许多研究表明，雌激素直接影响细胞功能，包括细胞因子的产生。巨噬细胞移动抑制因子（MIF）是一种参与妊娠的促炎细胞因子，特别是在胎盘形成的早期阶段。由于对小鼠的报告表明雌激素可调节 MIF，因此我们在此研究了雌激素对人胎盘 MIF 的影响。通过使用早孕绒毛膜绒毛外植体的体外模型，我们发现 17β-雌二醇（E2）能够以剂量依赖性方式调节 MIF 的释放（10-12 对 10-9 M，P <0.05；10-9 对 10-5 M，P <0.05；10-12 对 10-5 M，P <0.001）。与 MIF 释放不同，组织 MIF 蛋白或 MIF mRNA 没有明显变化。我们证明了 E2 浓度（10-9 和 10-5 M）可以作用于胎盘组织，下调参与 MIF 分泌的 ABC 转运蛋白 A1 的 mRNA 和蛋白表达。这些发现强调了激素和细胞因子之间的相互协作，并表明随着妊娠的进展，雌激素水平的升高可能在调节胎盘 MIF 分泌中起主要作用。
