长期输注白细胞介素-17会促进妊娠大鼠患高血压、细胞溶解性自然杀伤细胞活化及血管功能障碍。
Chronic infusion of interleukin-17 promotes hypertension, activation of cytolytic natural killer cells, and vascular dysfunction in pregnant rats.
作者信息
Travis Olivia K, White Dakota, Pierce W Austin, Ge Ying, Stubbs Cassandra Y, Spradley Frank T, Williams Jan M, Cornelius Denise C
机构信息
Department of Experimental Therapeutics and Pharmacologyogy, University of Mississippi Medical Center, Jackson, Mississippi.
Department of Emergency Medicine, University of Mississippi Medical Center, Jackson, Mississippi.
出版信息
Physiol Rep. 2019 Apr;7(7):e14038. doi: 10.14814/phy2.14038.
Previous studies by our lab have established that placental-ischemia stimulated T-helper 17 cells (T 17s) cause increased cytolytic natural killer (cNK) cell proliferation and activation during pregnancy; however, the exact mechanism is unknown. The objective of this study was to investigate the role of interlukin 17 (IL-17) in inducing cNK cell activation in pregnancy. We infused 150 pg/day of recombinant IL-17 into a subset of normal pregnant (NP) Sprague Dawley rats from gestation day (GD) 12-19 (NP+IL-17). On GD 19, mean arterial pressure (MAP), fetal and placental weights, cytokines, cNK cell activation, cytotoxic enzymes, and vascular reactivity were assessed. MAP significantly increased from 99 ± 3 mmHg in NP to 120 ± 1 mmHg in NP+IL-17 (P < 0.05). Fetal weight significantly decreased from 2.52 ± 0.04 g in NP to 2.32 ± 0.03 g in NP+IL-17 as did placental weight (NP: 0.65 ± 0.03 g; NP+IL-17: 0.54 ± 0.01 g, P < 0.05). Plasma levels of TNF-α increased to 281.4 ± 55.07 pg/mL in NP+IL-17 from 145.3 ± 16.03 pg/mL in NP (P < 0.05) while placental levels of VEGF decreased from 74.2 ± 6.48 pg/mg in NP to 54.2 ± 3.19 pg/mg in NP+IL-17. Total NK cells were increased in the placenta (NP: 14.3 ± 3.49%; NP+IL-17: 29.33 ± 2.76%, P < 0.05) as were cytolytic NK cells (NP: 3.31 ± 1.25%; NP+IL-17: 13.41 ± 1.81%, P < 0.05). A similar trend was observed in circulating NK cells. Plasma granzyme K increased from 3.55 ± 2.29 pg/mL in NP to 20.9 ± 7.76 pg/mL in NP+IL-17 (P < 0.05), and plasma granzyme B increased from 10.95 ± 0.64 pg/mL in NP to 14.9 ± 0.98 pg/mL in NP+IL-17(P < 0.05). In the placenta, both granzyme A (NP: 246.1 ± 16.7 pg/mg; NP+IL-17: 324.3 ± 15.07 pg/mg, P < 0.05) and granzyme B (NP: 15.18 ± 3.79 pg/mg; NP+IL-17: 27.25 ± 2.34 pg/mg, P < 0.05) increased in response to IL-17 infusion. Finally, vascular reactivity of uterine arteries was significantly impaired in response to IL-17 infusion. The results of this study suggest that IL-17 plays a significant role in the activation of cNK cells during pregnancy.
我们实验室之前的研究表明，胎盘缺血刺激的辅助性T细胞17（T17）会导致孕期细胞溶解性自然杀伤（cNK）细胞增殖和活化增加；然而，确切机制尚不清楚。本研究的目的是探讨白细胞介素17（IL-17）在孕期诱导cNK细胞活化中的作用。我们从妊娠第12天至第19天，每天向一部分正常妊娠（NP）的Sprague Dawley大鼠注入150 pg重组IL-17（NP+IL-17）。在妊娠第19天，评估平均动脉压（MAP）、胎儿和胎盘重量、细胞因子、cNK细胞活化、细胞毒性酶和血管反应性。MAP从NP组的99±3 mmHg显著升高至NP+IL-17组的120±1 mmHg（P<0.05）。胎儿体重从NP组的2.52±0.04 g显著降至NP+IL-17组的2.32±0.03 g，胎盘重量也有类似变化（NP组：0.65±0.03 g；NP+IL-17组：0.54±0.01 g，P<0.05）。NP+IL-17组血浆TNF-α水平从NP组的145.3±16.03 pg/mL升至281.4±55.07 pg/mL（P<0.05）；而胎盘VEGF水平从NP组的74.2±6.48 pg/mg降至NP+IL-17组的54.2±3.19 pg/mg。胎盘和循环中的NK细胞总数均增加（NP组：14.3±3.49%；NP+IL-17组：29.33±2.76%，P<0.05），细胞溶解性NK细胞也是如此（NP组：3.31±1.25%；NP+IL-17组：13.41±1.81%，P<0.05）。血浆颗粒酶K从NP组的3.55±2.29 pg/mL升至NP+IL-17组的20.9±7.76 pg/mL（P<0.05），血浆颗粒酶B从NP组的10.95±0.64 pg/mL升至NP+IL-17组的14.9±0.98 pg/mL（P<0.05）。在胎盘中，颗粒酶A（NP组：246.1±16.7 pg/mg；NP+IL-17组：324.3±15.07 pg/mg，P<0.05）和颗粒酶B（NP组：15.18±3.79 pg/mg；NP+IL-17组：27.25±2.34 pg/mg，P<0.05）在注入IL-17后均增加。最后，注入IL-17后子宫动脉的血管反应性显著受损。本研究结果表明，IL-17在孕期cNK细胞活化中起重要作用。
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