An increased population of regulatory T cells improves the pathophysiology of placental ischemia in a rat model of preeclampsia.
The reduced uterine perfusion pressure (RUPP) rat model of preeclampsia exhibits much of the pathology characterizing this disease, such as hypertension, inflammation, suppressed regulatory T cells (TRegs), reactive oxygen species (ROS), and autoantibodies to the ANG II type I receptor (AT1-AA) during pregnancy. The objective of this study was to determine whether supplementation of normal pregnant (NP) TRegs into RUPP rats would attenuate the pathophysiology associated with preeclampsia during pregnancy. CD4(+)/CD25(+) T cells were isolated from spleens of NP and RUPP rats, cultured, and injected into gestation day (GD) 12 normal pregnant rats that underwent the RUPP procedure on GD 14. On GD 1, mean arterial pressure (MAP) was recorded, and blood and tissues were collected for analysis. One-way ANOVA was used for statistical analysis. MAP increased from 99 ± 2 mmHg in NP (n = 12) to 127 ± 2 mmHg in RUPP (n = 21) but decreased to 118 ± 2 mmHg in RUPP+NP TRegs (n = 17). Circulating IL-6 and IL-10 were not significantly changed, while circulating TNF-α and IL-17 were significantly decreased after supplementation of TRegs. Placental and renal ROS were 339 ± 58.7 and 603 ± 88.1 RLU·min(-1)·mg(-1) in RUPP and significantly decreased to 178 ± 27.8 and 171 ± 55.6 RLU·min(-1)·mg(-1), respectively, in RUPP+NP TRegs; AT1-AA was 17.81 ± 1.1 beats per minute (bpm) in RUPP but was attenuated to 0.50 ± 0.3 bpm with NP TRegs. This study demonstrates that NP TRegs can significantly improve inflammatory mediators, such as IL-17, TNF-α, and AT1-AA, which have been shown to increase blood pressure during pregnancy.
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi; and.
Denise C
DC
Cornelius
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi; and.
Lorena M
LM
Amaral
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi; and.
Ashlyn
A
Harmon
Department of Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, Mississippi; and.
Kedra
K
Wallace
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi; and.
Alexia J
AJ
Thomas
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi; and.
Nathan
N
Campbell
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi; and.
Jeremy
J
Scott
Charité, Campus Buch, Experimental and Clinical Research Center and HELIOS Clinic Berlin-Buch, Berlin, Germany.
Florian
F
Herse
Charité, Campus Buch, Experimental and Clinical Research Center and HELIOS Clinic Berlin-Buch, Berlin, Germany.
Nadine
N
Haase
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi; and.
Janae
J
Moseley
Charité, Campus Buch, Experimental and Clinical Research Center and HELIOS Clinic Berlin-Buch, Berlin, Germany.
Gerd
G
Wallukat
Charité, Campus Buch, Experimental and Clinical Research Center and HELIOS Clinic Berlin-Buch, Berlin, Germany.
Ralf
R
Dechend
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi; and Department of Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, Mississippi; and bblamarca@umc.edu.
Babbette
B
LaMarca
D019264:Adoptive Transfer; D000818:Animals; D001794:Blood Pressure; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D007511:Ischemia / Q000473:pathology*; D010920:Placenta / Q000098:blood supply / Q000166:cytology / Q000473:pathology*; D011225:Pre-Eclampsia / Q000473:pathology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*
D016207:Cytokines; D019332:Endothelin-1; D012333:RNA, Messenger; D017382:Reactive Oxygen Species
hypertension; inflammation; oxidative stress; pregnancy; regulatory T cells