Preeclampsia, new onset hypertension with proteinuria during pregnancy, is associated with chronic inflammation and placental oxidative stress (ROS). Chronic interleukin-17 (IL-17) increases blood pressure, autoantibodies (angiotensin II type I receptor [AT1-AA]), and ROS during pregnancy. The objective of this study was to determine whether T-helper 17 (TH17) suppression via IL-17 recombinant receptor C (IL-17RC) decreases pathophysiology associated with placental ischemia (reduced uterine perfusion pressure [RUPP]). On gestation day 14, miniosmotic pumps infusing 100 pg of IL-17RC per day were implanted into pregnant rats undergoing RUPP. On gestation day 18, carotid catheters were inserted. On gestation day 19, mean arterial pressure was recorded and TH17 cells, oxidative stress, and AT1-AA were measured and analyzed via 1-way ANOVA. Mean arterial pressure increased from 101 ± 2 mm Hg in normal pregnant rats (n = 19) to 120 ± 1 mm Hg in RUPP rats (n = 17) but decreased to 110 ± 2 mm Hg in RUPP+IL-17RC rats (n = 22). Pup weight decreased from 2.28 ± 0.2 g in normal pregnant rats to 1.96 ± 0.3 g in RUPP rats but was significantly increased to 2.01 ± 0.1 in RUPP+IL-17RC rats. TH17 cells were 1.77% in RUPP rats but decreased to 0.65% in RUPP+IL-17RC rats. Urinary isoprostanes were normalized in RUPP+IL-17RC rats (52 pg/µg) compared with 89 pg/µg in RUPP controls. Placental ROS was 652 relative light units in RUPP rats but decreased to 337 relative light units in RUPP+IL-17RC rats. AT1-AA was 17.27 ± 0.7 bpm in RUPP rats but decreased to 5.00 ± 0.5 bpm in RUPP+IL-17RC rats. With this study, we show that infusion of IL-17RC blunts TH17s, oxidative stress, AT1-AA, and hypertension in the RUPP model of preeclampsia, indicating that TH17 cells may play an important role in disease pathophysiology.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3899693 | PMC |
| http://dx.doi.org/10.1161/HYPERTENSIONAHA.113.01514 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
RUPP Th17s cause hypertension and mitochondrial dysfunction in the kidney and placenta during pregnancy.
Pregnancy Hypertens
June 2023
Department of Pharmacology & Toxicology, University of Mississippi Medical Center, Jackson, MS, United States; Department of Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, MS, United States. Electronic address:
Background: Preeclampsia (PE), new-onset hypertension (HTN), and organ dysfunction during the second half of pregnancy, is associated with an increase in inflammatory immune cells, including T helper 17 (Th17) cells. Studies have demonstrated that mitochondrial (mt) dysfunction is important in the pathogenesis of PE though causative factors have yet to be fully identified. Although Th17 cells, natural killer (NK) cells, and mt dysfunction contribute to HTN in the reduced uterine perfusion pressure (RUPP) rat model, the role of Th17 cells or IL-17 in mt dysfunction is unknown.
View Article and Find Full Text PDFInterleukin-17 signaling mediates cytolytic natural killer cell activation in response to placental ischemia.
Am J Physiol Regul Integr Comp Physiol
June 2020
Department of Pharmacology, University of Mississippi Medical Center, Jackson, Mississippi.
T-helper (T)17s, IL-17, and cytolytic natural killer cells (cNKs) are increased in preeclampsia and contribute to the hypertension, inflammation, and fetal growth restriction that occurs in response to placental ischemia in the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia. As IL-17 stimulates NK cytotoxicity in vitro, we tested the hypothesis that IL-17 inhibition in RUPP rats would decrease cNK activation as a mechanism to improve maternal and fetal outcomes. On gestation (GD) , rats undergoing RUPP received a miniosmotic pump infusing IL-17RC (100 pg/day), a soluble IL-17 receptor (RUPP + IL-17RC).
View Article and Find Full Text PDFAdministration of interleukin-17 soluble receptor C suppresses TH17 cells, oxidative stress, and hypertension in response to placental ischemia during pregnancy.
Hypertension
December 2013
Maternal Fetal Medicine Fellowship Program, Department of Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, MS 39216.
Preeclampsia, new onset hypertension with proteinuria during pregnancy, is associated with chronic inflammation and placental oxidative stress (ROS). Chronic interleukin-17 (IL-17) increases blood pressure, autoantibodies (angiotensin II type I receptor [AT1-AA]), and ROS during pregnancy. The objective of this study was to determine whether T-helper 17 (TH17) suppression via IL-17 recombinant receptor C (IL-17RC) decreases pathophysiology associated with placental ischemia (reduced uterine perfusion pressure [RUPP]).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!