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.
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。