Inhibition of Caspase 1 Reduces Blood Pressure, Cytotoxic NK Cells, and Inflammatory T-Helper 17 Cells in Placental Ischemic Rats.
Inhibition of Caspase 1 Reduces Blood Pressure, Cytotoxic NK Cells, and Inflammatory T-Helper 17 Cells in Placental Ischemic Rats.
复制标题
DOI：
10.3390/ijms25020863
复制
发表时间：
2024-01-10
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
先兆子痫（PE）的特征在于母体高血压、胎儿生长受限（FGR）、以及炎症和细胞毒性NK细胞（cNK）和炎性T辅助细胞17（TH 17）的群体增加。细胞毒性NK细胞和TH 17细胞都受到IL-1β信号传导的严重影响。Caspase 1活性导致炎性细胞因子IL-1β的释放，其在PE女性中增加。因此，我们测试了以下假设：在子宫灌注压降低（RUPP）的大鼠中，VX-765对胱天蛋白酶1的抑制将减弱PE病理生理学。在妊娠第14天（GD），定时妊娠Sprague-Dawley大鼠接受RUPP或Sham程序，并分成接受溶媒或VX-765（50 mg/kg/天i. p.）的组。在GD 19，通过颈动脉导管测量MAP，并收集血液和组织。对胎盘组织进行生物染色和流式细胞术分析。与Sham大鼠相比，RUPP大鼠的胎盘IL-1β增加，VX-765处理降低了RUPP大鼠的IL-1β。与溶剂处理的RUPP大鼠相比，半胱天冬酶1抑制减少了RUPP大鼠的胎盘cNK和TH 17。与Sham大鼠相比，在RUPP大鼠中观察到MAP增加，并且在RUPP + VX-765大鼠中降低。与Sham大鼠相比，RUPP大鼠胎盘活性氧（ROS）升高。VX-765给药减少了治疗的RUPP大鼠中的ROS。半胱天冬酶1抑制增加了治疗组活幼崽的数量，但对胎儿体重或胎盘效率没有影响。总之，半胱天冬酶1抑制减少了胎盘IL-1β、炎性TH 17和cNK群体，并降低了RUPP大鼠的MAP。这些数据表明，Caspase 1是PE病理生理学的关键贡献者。这需要进一步研究Caspase 1作为改善PE中母体结局的潜在治疗靶点。
Preeclampsia (PE) is characterized by maternal hypertension, fetal growth restriction (FGR), and increased inflammation and populations of cytotoxic NK cells (cNKs) and inflammatory T-Helper 17 cells (TH17s). Both cytotoxic NK cells and TH17 cells are heavily influenced via IL-1β signaling. Caspase 1 activity leads to the release of the inflammatory cytokine IL-1β, which is increased in women with PE. Therefore, we tested the hypothesis that the inhibition of Caspase 1 with VX-765 in rats with reduced uterine perfusion pressure (RUPP) will attenuate PE pathophysiology. On gestation day (GD) 14, timed pregnant Sprague–Dawley rats underwent the RUPP or Sham procedure and were separated into groups that received either vehicle or VX-765 (50 mg/kg/day i.p.). On GD19, MAP was measured via carotid catheter and blood and tissues were collected. Bio-Plex and flow cytometry analysis were performed on placental tissues. Placental IL-1β was increased in the RUPP rats vs. the Sham rats and treatment with VX-765 reduced IL-1β in the RUPP rats. Caspase 1 inhibition reduced placental cNKs and TH17s in RUPP rats compared to vehicle-treated RUPP rats. Increased MAP was observed in RUPP rats compared with Sham rats and was reduced in RUPP + VX-765 rats. Placental reactive oxygen species (ROS) were elevated in RUPP rats compared to Sham rats. VX-765 administration reduced ROS in treated RUPP rats. Caspase 1 inhibition increased the number of live pups, yet had no effect on fetal weight or placental efficiency in the treated groups. In conclusion, Caspase 1 inhibition reduces placental IL-1β, inflammatory TH17 and cNK populations, and reduces MAP in RUPP rats. These data suggest that Caspase 1 is a key contributor to PE pathophysiology. This warrants further investigation of Caspase 1 as a potential therapeutic target to improve maternal outcomes in PE.
登录
查看更多内容
影响因子：
9
作者：
Dhani S;Zhao Y;Zhivotovsky B
通讯作者：
Zhivotovsky B
影响因子：
3.7
作者：
Lasiglie, Denise;Traggiai, Elisabetta;Gattorno, Marco
通讯作者：
Gattorno, Marco
DOI：
10.1042/cs20171118
发表时间：
2017-12-01
期刊：
Clinical science (London, England : 1979)
影响因子：
--
作者：
Elfarra J;Amaral LM;McCalmon M;Scott JD;Cunningham MW Jr;Gnam A;Ibrahim T;LaMarca B;Cornelius DC
通讯作者：
Cornelius DC
影响因子：
32.4
作者：
Dupaul-Chicoine, Jeremy;Arabzadeh, Azadeh;Saleh, Maya
通讯作者：
Saleh, Maya
影响因子：
3.4
作者：
Lu, Mudan;Ma, Fengying;Chen, Daozhen
通讯作者：
Chen, Daozhen