Abstract P101: Interleukin 17 Signaling Mediates Cytolytic Natural Killer Cell Activation in Response to Placental Ischemia

Autor:	Denise C. Cornelius, Jan M. Williams, Willie L. Thompson, Dakota White, Olivia K. Travis, Babbette LaMarca, Cedar H. Baik, Chelsea Giachelli
Rok vydání:	2019
Předmět:	medicine.medical_specialty Pregnancy business.industry Rat model Ischemia Inflammation medicine.disease Preeclampsia Cytolysis Endocrinology Internal medicine Internal Medicine medicine Interleukin 17 medicine.symptom business Natural killer cell activation
Zdroj:	Hypertension. 74
ISSN:	1524-4563 0194-911X
DOI:	10.1161/hyp.74.suppl_1.p101
Popis:	The R educed U terine P erfusion P ressure (RUPP) rat model of placental ischemia mimics many characteristics of preeclampsia (PE) including hypertension, fetal growth restriction, and increased T H 17s, IL-17, and cytolytic natural killer cells (cNKs). IL-17 stimulates NK cytotoxicity in vitro . This study tested the hypothesis that blockade of IL-17 signaling would inhibit activation of cNKs to improve blood pressure and fetal growth in RUPP rats. On gestation day (GD) 14, osmotic pumps infusing IL-17 RC (100 pg/d), a soluble receptor for IL-17, were implanted into pregnant rats undergoing RUPP (RUPP+IL17 RC). On GD 19, circulating and placental T H 17s and cNKs were quantified via flow cytometry in normal pregnant (NP), RUPP, and RUPP+IL17 RC rats. cNK activation, placental ROS, fetal and placental weights, and MAP were also assessed. As we have previously shown, placental T H 17 populations (% gated) were significantly increased in RUPP (23.1±3.9%, n=9) compared to NP (8.5±3.9%, n=9) rats and were suppressed in RUPP+IL17 RC (8.3±3.1%, n=9). Circulating T H 17s followed the same trend. Placental cNKs, significantly increased from 7.2±2.8% in NP to 16.6±3.3% in RUPP, and were normalized to 7.2±2.8% after IL-17 blockade (pin vitro cytotoxic activity of placental NK cells from rats in each group demonstrated a 5-fold increase in cytotoxicity by RUPP NK cells compared to NP NK cells. This was blunted in NK cells from RUPP+IL17 RC rats. Placental ROS was increased in RUPP compared to NP and significantly decreased with IL-17 blockade. Fetal weight decreased from 2.4±0.04 g in NP to 2.1±0.04 g in RUPP and increased to 2.3±0.05 g in RUPP+IL17 RC (p
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::b003548b55813835e5a3f0057a80b5df https://doi.org/10.1161/hyp.74.suppl_1.p101 Zobrazit plný text záznamu