Department of Hematology, Provincial Hospital Affiliated to Shandong University, Shandong, 250012, PR China.
Mol Med Rep. 2011 Jan-Feb;4(1):53-8. doi: 10.3892/mmr.2010.395. Epub 2010 Nov 5.
Preeclampsia is a complex multi-organ disease and the leading cause of maternofetal morbidity and mortality. Low levels of indoleamine 2,3-dioxygenase (IDO) and diminished numbers of regulatory T cells (Tregs) have been separately reported to participate in the pathogenesis of preeclampsia. In the present study, we aimed to determine whether alterations in the expression of IDO, forkhead box P3 (Foxp3) and interleukin-18 (IL-18) contribute to the pathogenesis of preeclampsia, by measuring their levels in preeclamptic placentae and in placentae from healthy pregnant women as a control. IDO protein levels were determined by immunohistochemistry, while the mRNA levels of IDO, FoxP3 and IL-18 were measured by quantitative RT-PCR. The intensity of IDO immunostaining was lower in the preeclamptic placentae than in the normal controls, and was related to the clinical severity of the preeclampsia. Quantitative RT-PCR revealed that the IDO and IL-18 mRNA levels were reduced in a correlated manner the preeclamptic placentae compared to the controls, and that the levels of FoxP3 mRNA were consistently decreased in the preeclamptic group. A positive correlation betwen FoxP3 and IDO mRNA was found. The results of the study indicate that IL-18, IDO and FoxP3 mRNA levels were decreased in the preeclamptic placentae. Reduced IDO levels in preeclampsia may be partly influenced by IL-18, and result in the maladaptation of maternal tolerance and the pathogenesis of preeclampsia by directly reducing Tregs.
子痫前期是一种复杂的多器官疾病，也是孕产妇发病率和死亡率的主要原因。已有研究分别报道，色氨酸 2,3-双加氧酶（IDO）水平降低和调节性 T 细胞（Tregs）数量减少参与子痫前期的发病机制。在本研究中，我们旨在通过测量子痫前期胎盘和正常妊娠妇女胎盘组织中 IDO、叉头框 P3（Foxp3）和白细胞介素-18（IL-18）的表达水平，确定其表达改变是否有助于子痫前期的发病机制。采用免疫组织化学法检测 IDO 蛋白水平，实时定量 RT-PCR 法检测 IDO、Foxp3 和 IL-18 的 mRNA 水平。IDO 免疫染色强度在子痫前期胎盘组织中低于正常对照组，且与子痫前期的临床严重程度相关。实时定量 RT-PCR 结果显示，与对照组相比，子痫前期胎盘组织中 IDO 和 IL-18 的 mRNA 水平呈相关性降低，Foxp3 mRNA 水平持续降低。Foxp3 和 IDO mRNA 之间存在正相关。研究结果表明，子痫前期胎盘组织中 IL-18、IDO 和 Foxp3 mRNA 水平降低。子痫前期 IDO 水平降低可能部分受 IL-18 影响，通过直接减少 Tregs 导致母体耐受失调和子痫前期发病。
