期刊
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
卷 315, 期 2, 页码 R336-R343出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00061.2018
关键词
hypertension; natural killer cell; oxidative stress; pregnancy; T-helper 17
类别
资金
- National Institutes of Health [HL-130456, HD-067541, GM-104357, DK-109133]
Previous studies have demonstrated that T-helper 17 (T(H)17) cells and cytolytic natural killer (cNK) cells are increased in women with preeclampsia. In this study we investigated the role of placental ischemia-stimulated T(H)17 cells in induction of cNK cells in pregnancy. We further assessed the role of T(H)17 cell-mediated oxidative stress in facilitation of cNK cell activation in pregnancy by treating rats with the SOD mimetic tempol. CD4(+)/CD25(-) cells were isolated from reduced uterine perfusion pressure (RUPP) rats and differentiated into T(H)17 cells in vitro. On day 12 of gestation (GD12), 1 X 10(6) placental ischemia-stimulated T(H)17 cells were injected into normal pregnant (NP) rats (NP + RUPP T(H)17 rats), and a subset of rats were treated with tempol (30 mg.kg(-1).day(-1)) from GD12 to GD19 (NP + RUPP T(H)17 + tempol rats). On GD19, cNK cells, mean arterial pressure, fetal weight, and cNK cell-associated cytokines and proteins were measured. Placental cNK cells were 2.9 +/- 1, 14.9 +/- 4, and 2.8 +/- 1.0% gated in NP, NP + RUPP T(H)17, and NP + RUPP T(H)17 + tempol rats, respectively. Mean arterial pressure increased from 96 +/- 5 mmHg in NP rats to 118 +/- 2 mmHg in NP + RUPP T(H)17 rats and was 102 +/- 3 mmHg in NP + RUPP T(H)17 + tempol rats. Fetal weight was 2.37 +/- 0.04, 1.95 +/- 0.14, and 2.3 +/- 0.05 g in NP, NP + RUPP T(H)17, and NP + RUPP T(H)17 + tempol rats, respectively. Placental IFN gamma increased from 1.1 +/- 0.6 pg/mg in NP rats to 3.9 +/- 0.6 pg/mg in NP + RUPP T(H)17 rats. Placental perforin increased from 0.18 +/- 0.18 pg/mg in NP rats to 2.4 +/- 0.6 pg/mg in NP + RUPP T(H)17 rats. Placental levels of granzymes A and B followed a similar pattern. Treatment with tempol did not lower placental cNK cytokines or proteins. The results of the present study identify T(H)17 cells as a mediator of aberrant NK cell activation that is associated with preeclampsia.
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