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Abstract：
OBJECTIVE: Preeclampsia (PE) is a hypertensive pregnancy disorder that is a leading cause of maternal and fetal morbidity and mortality characterized by maternal vascular dysfunction, oxidative stress, chronic immune activation, and excessive inflammation. No cure exists beyond delivery of the fetal-placental unit and the mechanisms driving pathophysiology are not fully understood. However, aberrant immune responses have been extensively characterized in clinical studies and shown to mediate PE pathophysiology in animal studies. One pathway that may mediate aberrant immune responses in PE is deficiencies in the IL-33 signaling pathway. In this study, we aim to investigate the impact of IL-33 signaling inhibition on cNK, TH17, and TReg populations, vascular function, and maternal blood pressure during pregnancy.
METHODS: In this study, IL-33 signaling was inhibited using two different methods: intraperitoneal administration of recombinant ST2 (which acts as a decoy receptor for IL-33) and administration of a specific IL-33 neutralizing antibody. Maternal blood pressure, uterine artery resistance index, renal and placental oxidative stress, cNK, TH17, and TReg populations, various cytokines, and pre-proendothelin-1 levels were measured.
RESULTS: IL-33 signaling inhibition increased maternal blood pressure, uterine artery resistance, placental and renal oxidative stress. IL-33 signaling inhibition also increased placental cNK and TH17 and renal TH17 cells while decreasing placental TReg populations. IL-33 neutralization increased circulating cNK and TH17s and decreased circulating TRegs in addition to increasing pre-proendothelin-1 levels.
CONCLUSIONS: Data presented in this study demonstrate a role for IL-33 signaling in controlling vascular function and maternal blood pressure during pregnancy possibly by mediating innate and adaptive immune inflammatory responses, identifying the IL-33 signaling pathway as a potential therapeutic target for managing preeclampsia.
METHODS: In this study, IL-33 signaling was inhibited using two different methods: intraperitoneal administration of recombinant ST2 (which acts as a decoy receptor for IL-33) and administration of a specific IL-33 neutralizing antibody. Maternal blood pressure, uterine artery resistance index, renal and placental oxidative stress, cNK, TH17, and TReg populations, various cytokines, and pre-proendothelin-1 levels were measured.
RESULTS: IL-33 signaling inhibition increased maternal blood pressure, uterine artery resistance, placental and renal oxidative stress. IL-33 signaling inhibition also increased placental cNK and TH17 and renal TH17 cells while decreasing placental TReg populations. IL-33 neutralization increased circulating cNK and TH17s and decreased circulating TRegs in addition to increasing pre-proendothelin-1 levels.
CONCLUSIONS: Data presented in this study demonstrate a role for IL-33 signaling in controlling vascular function and maternal blood pressure during pregnancy possibly by mediating innate and adaptive immune inflammatory responses, identifying the IL-33 signaling pathway as a potential therapeutic target for managing preeclampsia.
摘要：
目的：先兆子痫（PE）是一种高血压妊娠疾病，是以母体血管功能障碍为特征的母体和胎儿发病率和死亡率的主要原因，氧化应激，慢性免疫激活，过度的炎症。除了胎儿胎盘单位的分娩之外，没有治愈方法，并且驱动病理生理学的机制尚未完全了解。然而,异常免疫应答在临床研究中得到了广泛的表征,并在动物研究中显示出介导PE病理生理学的作用。可在PE中介导异常免疫应答的一个途径是IL-33信号传导途径中的缺陷。在这项研究中,我们的目的是研究IL-33信号抑制对cNK，TH17和TReg人口，血管功能,和孕妇在怀孕期间的血压。
方法：在本研究中，使用两种不同的方法抑制IL-33信号传导:腹膜内施用重组ST2(其充当IL-33的诱饵受体)和施用特异性IL-33中和抗体。产妇血压,子宫动脉阻力指数,肾脏和胎盘氧化应激，cNK,TH17和TReg人口，各种细胞因子，测量前内皮素-1水平。
结果：IL-33信号抑制增加母体血压，子宫动脉阻力，胎盘和肾脏氧化应激。IL-33信号传导抑制还增加胎盘cNK和TH17以及肾TH17细胞,同时减少胎盘TReg群体。IL-33中和除了增加前内皮素-1水平外，还增加了循环的cNK和TH17，并减少了循环的TReg。
结论：本研究中提供的数据表明，IL-33信号在控制妊娠期间的血管功能和母体血压中的作用可能通过介导先天和适应性免疫炎症反应，确定IL-33信号通路作为控制先兆子痫的潜在治疗靶标。
方法：在本研究中，使用两种不同的方法抑制IL-33信号传导:腹膜内施用重组ST2(其充当IL-33的诱饵受体)和施用特异性IL-33中和抗体。产妇血压,子宫动脉阻力指数,肾脏和胎盘氧化应激，cNK,TH17和TReg人口，各种细胞因子，测量前内皮素-1水平。
结果：IL-33信号抑制增加母体血压，子宫动脉阻力，胎盘和肾脏氧化应激。IL-33信号传导抑制还增加胎盘cNK和TH17以及肾TH17细胞,同时减少胎盘TReg群体。IL-33中和除了增加前内皮素-1水平外，还增加了循环的cNK和TH17，并减少了循环的TReg。
结论：本研究中提供的数据表明，IL-33信号在控制妊娠期间的血管功能和母体血压中的作用可能通过介导先天和适应性免疫炎症反应，确定IL-33信号通路作为控制先兆子痫的潜在治疗靶标。
