title: Endothelin-1 is not a Mechanism of IL-17 Induced Hypertension during Pregnancy.
abstract: Preeclampsia is characterized as new onset maternal hypertension and proteinuria after 20 weeks gestation. Studies suggest that endothelin (ET-1) is a regulator of vascular function in preeclampsia and plays a major role in mediating chronic reduction in uterine perfusion pressure (RUPP)-induced hypertension. We recently demonstrated a role for the autoimmune cytokine interleukin 17 (IL-17) in causing placental oxidative stress and hypertension during pregnancy. In this current study, we investigated the role of ET-1 as a potential mechanism by which TH17 cells and IL-17 mediate hypertension in preeclampsia. While IL-17 infusion into normal pregnant rats increased blood pressure in a dose-responsive manner (98+/-2 mmHg in NP (n=20) to 105+/-3 mmHg in IL-17 (50pg/day, n=20) to 120+/-4 mmHg in IL-17 (100pg/day, n=10) to 123+/-3 mmHg in IL-17 (150 pg/day, n=7), it decreased local endothelin in placentas (NP (n=10) 7.5±0.3; IL-17 (100 pg/day, n=5) 6.4±0.2; IL-17 (150 pg/day, n=12) 4.5+1.5) and renal cortices (NP (n=8) 7.9 + 0.4; IL-17 (100 pg/day, n=6) 7.1±0.4; IL-17 (150 pg/day, n=4) 1.6 +0.7 during pregnancy. In addition, increasing IL-17 directly reduced secretion of ET-1 by human umbilical venous endothelial cells (HUVECs). HUVEC ET-1 secretion decreased from that seen in serum free media 42.7±7.7 pg/ml to 36.2 ± 5.9 pg/ml at 10 pg IL-17 to 31.3 ± 5.1 pg/ml at 10 μg IL-17. Our observations suggest that IL-17 negatively regulates the ET-1 pathway in local tissues and cultured endothelial cells and that the ET-1 pathway is not a mechanism by which IL-17 causes hypertension during pregnancy.
authors.affiliation: Department of Pharmacology & Obstetrics & Gynecology, University of Mississippi Medical Center, USA.
authors.forename: Denise C
authors.initials: DC
authors.lastname: Cornelius
authors.affiliation: Department of Pharmacology & Obstetrics & Gynecology, University of Mississippi Medical Center, USA.
authors.forename: Kedra
authors.initials: K
authors.lastname: Wallace
authors.affiliation: Department of Pharmacology & Obstetrics & Gynecology, University of Mississippi Medical Center, USA.
authors.forename: Luissa
authors.initials: L
authors.lastname: Kiprono
authors.affiliation: Department of Pharmacology & Obstetrics & Gynecology, University of Mississippi Medical Center, USA.
authors.forename: Pushpinder
authors.initials: P
authors.lastname: Dhillon
authors.affiliation: Department of Pharmacology & Obstetrics & Gynecology, University of Mississippi Medical Center, USA.
authors.forename: Janae
authors.initials: J
authors.lastname: Moseley
authors.affiliation: Department of Pharmacology & Obstetrics & Gynecology, University of Mississippi Medical Center, USA.
authors.forename: Babbette
authors.initials: B
authors.lastname: LaMarca