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Blunting Circulating TH17 cells Decreases Hypertension and Oxidative Stress in Response to Placental Ischemia
Author(s) -
Cornelius Denise C,
Hogg James P,
Wallace Kedra,
Moseley Janae,
LaMarca Babbette
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1115.4
Subject(s) - oxidative stress , preeclampsia , medicine , endocrinology , blood pressure , pregnancy , biology , genetics
Preeclampsia (PE), new onset hypertension with proteinuria during pregnancy, is associated with chronic inflammation and placental oxidative stress (ROS). We have shown that chronic IL‐17 increases blood pressure and placental ROS during pregnancy. The objective of this study was to determine if TH17 blockade via IL‐17RC (recombinant receptor C) decreases hypertension and placental ROS in response to placental ischemia. On day 14 of gestation, mini‐osmotic pumps infusing 100 pg/day of IL‐17RC were implanted into pregnant rats undergoing RUPP (Reduced Uterine Perfusion Pressure). On gestation day18 carotid catheters were inserted and on day 19 blood pressure (MAP) was recorded, TH17 cells measured from peripheral blood leukocytes using flow cytometry, and placental ROS detected by chemiluminescence. One‐way ANOVA was used for statistical analysis. MAP increased from 101 ±3 mmHg in NP (n=18), to 118±4 mmHg in RUPP (n=21), decreased to 107±5 mmHg in RUPP+IL‐17RC rats (n=14). TH17 cells increased from 0.196 ± 0.1% in NP to 2.311 ± 1.2% in RUPP, and decreased to 1.003 ± 0.3% in RUPP+IL‐17RC rats. Placental ROS increased from 410 RLU in NP to 609 RLU in RUPP, but decreased to 511 RLU in RUPP+IL‐17RC rats. Infusion of IL‐17RC blunted TH17 cells, placental oxidative stress, and hypertension in the RUPP rat model of PE indicating that TH17 cell activation may play an important role in oxidative stress and hypertension during PE. This work was supported by NIH grants RO1HD067541 and T32HL105324