Administration of interleukin-17 soluble receptor C suppresses TH17 cells, oxidative stress, and hypertension in response to placental ischemia during pregnancy.
Administration of interleukin-17 soluble receptor C suppresses TH17 cells, oxidative stress, and hypertension in response to placental ischemia during pregnancy.
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DOI：
10.1161/hypertensionaha.113.01514
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发表时间：
2013-12
期刊：
影响因子：
--
通讯作者：
LaMarca B
中科院分区：
文献类型：
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作者：
Cornelius DC;Hogg JP;Scott J;Wallace K;Herse F;Moseley J;Wallukat G;Dechend R;LaMarca B
先兆子痫（PE）是妊娠期新发高血压合并蛋白尿，与慢性炎症和胎盘氧化应激（ROS）有关。妊娠期慢性IL-17升高血压（MAP）、自身抗体（AT1-AA）和ROS。本研究的目的是确定通过IL-17RC（重组受体C）抑制TH17是否会降低与胎盘缺血（RUPP）相关的病理生理。在妊娠第14天，将IL-17RC灌注100 pg/d的微渗透泵植入妊娠第18天的颈动脉导管，记录第19天的MAP，测量TH17细胞、氧化应激和AT1-AA，并采用单因素方差分析。正常妊娠、NP组（n=19） MAP升高至120±1 mmHg (n=17)， RUPP+IL-17RC组（n=22） MAP下降至110±2 mmHg。RUPP组幼仔体重从NP组的2.28±0.2 g降至RUPP组的1.96±0.3 g，而RUPP+IL-17RC组的幼仔体重则显著增加至2.01±0.1 g。RUPP+IL-17RC大鼠TH17细胞为1.77%，而RUPP+IL-17RC大鼠TH17细胞为0.65%。RUPP +IL-17RC大鼠尿异前列腺素正常化（52 pg/μg），而RUPP对照组为89 pg/μg。RUPP+IL-17RC大鼠胎盘ROS为652 RLU，而RUPP+IL-17RC大鼠胎盘ROS为337 RLU。RUPP+IL-17RC大鼠的AT1-AA为17.27±0.7 bpm，而RUPP+IL-17RC大鼠的AT1-AA为5.00±0.5 bpm。通过本研究，我们发现IL-17RC在PE RUPP模型中可使TH17细胞、氧化应激、AT1-AA和高血压发生钝化，提示TH17细胞可能在疾病病理生理中发挥重要作用。
Pre-eclampsia (PE), new onset hypertension with proteinuria during pregnancy, is associated with chronic inflammation and placental oxidative stress (ROS). Chronic IL-17 increases blood pressure (MAP), autoantibodies (AT1-AA) and ROS during pregnancy. The objective of this study was to determine if TH17 suppression via IL-17RC (recombinant receptor C) decreases pathophysiology associated with placental ischemia (RUPP). On gestation day 14, mini-osmotic pumps infusing 100 pg/day of IL-17RC were implanted into pregnant rats undergoing RUPP (Reduced Uterine Perfusion Pressure), gestation day18 carotid catheters were inserted, day 19 MAP was recorded, TH17 cells, oxidative stress and AT1-AA were measured and analyzed via one-way ANOVA. MAP increased from 101 ±2 mmHg in normal pregnant, NP (n=19), to 120 ±1 mmHg in RUPP (n=17),but decreased to 110±2 mmHg in RUPP+IL-17RC rats (n=22). Pup weight decreased from 2.28 ± 0.2 g in NP to 1.96 ± 0.3 g in RUPP rats, but was significantly increased to 2.01 ± 0.1 in RUPP+IL-17RC rats. TH17 cells were 1.77% in RUPP but decreased to 0.65% in RUPP+IL-17RC rats. Urinary isoprostanes normalized in RUPP +IL-17RC rats (52 pg/μg) compared to 89 pg/μg in RUPP controls. Placental ROS was 652 RLU in RUPP, but decreased to 337 RLU in RUPP+IL-17RC rats. AT1-AA was 17.27 ± 0.7 bpm in RUPP but decreased to 5.00 ± 0.5 bpm in RUPP+IL-17RC rats. With this study, we show that infusion of IL-17RC blunts TH17s, oxidative stress, AT1-AA, and hypertension in the RUPP model of PE indicating that TH17 cells may play an important role in disease pathophysiology.