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Original Article

Administration of Interleukin-17 Soluble Receptor C Suppresses TH17 Cells, Oxidative Stress, and Hypertension in Response to Placental Ischemia During Pregnancy

Denise C. Cornelius, James P. Hogg, Jeremy Scott, Kedra Wallace, Florian Herse, Janae Moseley, Gerd Wallukat, Ralf Dechend, Babbette LaMarca
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https://doi.org/10.1161/HYPERTENSIONAHA.113.01514
Hypertension. 2013;HYPERTENSIONAHA.113.01514
Originally published September 23, 2013
Denise C. Cornelius
Departments of Pharmacology & Toxicology (D.C.C., J.S., J.M., B.L. ) and Obstetrics & Gynecology (J.P.H., K.W., B.L.), University of Mississippi Medical Center, Jackson, MS; and Experimental and Clinical Research Center and Max-Delbrück Center for Molecular Medicine and HELIOS Clinic-Berlin, Germany (F.H., G.W., R.D.).
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James P. Hogg
Departments of Pharmacology & Toxicology (D.C.C., J.S., J.M., B.L. ) and Obstetrics & Gynecology (J.P.H., K.W., B.L.), University of Mississippi Medical Center, Jackson, MS; and Experimental and Clinical Research Center and Max-Delbrück Center for Molecular Medicine and HELIOS Clinic-Berlin, Germany (F.H., G.W., R.D.).
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Jeremy Scott
Departments of Pharmacology & Toxicology (D.C.C., J.S., J.M., B.L. ) and Obstetrics & Gynecology (J.P.H., K.W., B.L.), University of Mississippi Medical Center, Jackson, MS; and Experimental and Clinical Research Center and Max-Delbrück Center for Molecular Medicine and HELIOS Clinic-Berlin, Germany (F.H., G.W., R.D.).
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Kedra Wallace
Departments of Pharmacology & Toxicology (D.C.C., J.S., J.M., B.L. ) and Obstetrics & Gynecology (J.P.H., K.W., B.L.), University of Mississippi Medical Center, Jackson, MS; and Experimental and Clinical Research Center and Max-Delbrück Center for Molecular Medicine and HELIOS Clinic-Berlin, Germany (F.H., G.W., R.D.).
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Florian Herse
Departments of Pharmacology & Toxicology (D.C.C., J.S., J.M., B.L. ) and Obstetrics & Gynecology (J.P.H., K.W., B.L.), University of Mississippi Medical Center, Jackson, MS; and Experimental and Clinical Research Center and Max-Delbrück Center for Molecular Medicine and HELIOS Clinic-Berlin, Germany (F.H., G.W., R.D.).
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Janae Moseley
Departments of Pharmacology & Toxicology (D.C.C., J.S., J.M., B.L. ) and Obstetrics & Gynecology (J.P.H., K.W., B.L.), University of Mississippi Medical Center, Jackson, MS; and Experimental and Clinical Research Center and Max-Delbrück Center for Molecular Medicine and HELIOS Clinic-Berlin, Germany (F.H., G.W., R.D.).
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Gerd Wallukat
Departments of Pharmacology & Toxicology (D.C.C., J.S., J.M., B.L. ) and Obstetrics & Gynecology (J.P.H., K.W., B.L.), University of Mississippi Medical Center, Jackson, MS; and Experimental and Clinical Research Center and Max-Delbrück Center for Molecular Medicine and HELIOS Clinic-Berlin, Germany (F.H., G.W., R.D.).
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Ralf Dechend
Departments of Pharmacology & Toxicology (D.C.C., J.S., J.M., B.L. ) and Obstetrics & Gynecology (J.P.H., K.W., B.L.), University of Mississippi Medical Center, Jackson, MS; and Experimental and Clinical Research Center and Max-Delbrück Center for Molecular Medicine and HELIOS Clinic-Berlin, Germany (F.H., G.W., R.D.).
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Babbette LaMarca
Departments of Pharmacology & Toxicology (D.C.C., J.S., J.M., B.L. ) and Obstetrics & Gynecology (J.P.H., K.W., B.L.), University of Mississippi Medical Center, Jackson, MS; and Experimental and Clinical Research Center and Max-Delbrück Center for Molecular Medicine and HELIOS Clinic-Berlin, Germany (F.H., G.W., R.D.).
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Abstract

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.

  • hypertension
  • inflammation
  • oxidative stress
  • pregnancy
  • Received April 4, 2013.
  • Revision received April 17, 2013.
  • Accepted August 23, 2013.
  • © 2013 American Heart Association, Inc.
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    Administration of Interleukin-17 Soluble Receptor C Suppresses TH17 Cells, Oxidative Stress, and Hypertension in Response to Placental Ischemia During Pregnancy
    Denise C. Cornelius, James P. Hogg, Jeremy Scott, Kedra Wallace, Florian Herse, Janae Moseley, Gerd Wallukat, Ralf Dechend and Babbette LaMarca
    Hypertension. 2013;HYPERTENSIONAHA.113.01514, originally published September 23, 2013
    https://doi.org/10.1161/HYPERTENSIONAHA.113.01514

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    Administration of Interleukin-17 Soluble Receptor C Suppresses TH17 Cells, Oxidative Stress, and Hypertension in Response to Placental Ischemia During Pregnancy
    Denise C. Cornelius, James P. Hogg, Jeremy Scott, Kedra Wallace, Florian Herse, Janae Moseley, Gerd Wallukat, Ralf Dechend and Babbette LaMarca
    Hypertension. 2013;HYPERTENSIONAHA.113.01514, originally published September 23, 2013
    https://doi.org/10.1161/HYPERTENSIONAHA.113.01514
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