Jeff Shaw1, Zhonghua Tang1, Henning Schneider2, Karen Saljé3, Stefan R Hansson4, Seth Guller5. 1. Obstetrics, Gynecology, & Reproductive Sciences, Yale School of Medicine, United States. 2. Department of Obstetrics & Gynecology, Inselspital, Bern University Hospital, University of Bern, Switzerland. 3. OB/GYN, Institute of Clinical Sciences, Lund University, Lund, Sweden; Department of Clinical Pharmacology, University Medicine, Greifswald, Germany. 4. OB/GYN, Institute of Clinical Sciences, Lund University, Lund, Sweden. 5. Obstetrics, Gynecology, & Reproductive Sciences, Yale School of Medicine, United States. Electronic address: seth.guller@yale.edu.
Abstract
INTRODUCTION: There is a consensus that factors released by the placenta to maternal circulation, including TNF-α, play a key role in activating the maternal endothelium in pregnancies with preeclampsia (PE). Dual perfusion preserves the structural organization of the placenta to a greater degree than other in vitro systems and has been used by our group and others to examine placental pathophysiology associated with PE. The objective of this study was to use the dual perfusion model to test whether TNF-α released by the placenta to maternal perfusate affects pro-inflammatory cytokine secretion by, and activation of, endothelial cells, thereby furthering our understanding of placental and endothelial dysfunction in PE. METHOD: We used maternal perfusate, two endothelial cell lines (HUVECs and HEECs), and a TNF-α blocking antibody to test whether placental-derived TNF-α plays a significant role in altering the expression and secretion of pro-inflammatory cytokines in endothelial cells as well as the expression of activation markers in this cell type. RESULTS: The presence of maternal perfusate significantly enhanced IL-6, IL-8, and MCP-1 secretion, levels of their mRNA, as well as mRNA levels of markers of endothelial activation (E-selectin, ICAM-1, and VCAM-1). The addition of a TNF-α blocking antibody significantly inhibited the maternal perfusate-mediated enhancement of cytokine secretion by, and expression of activation markers, in both HUVECs and HEECs. DISCUSSION: These results demonstrate that TNF-α significantly contributed to endothelial cell pro-inflammatory cytokine secretion and activation suggesting that blocking TNF-α action may mitigate the effects of maternal endothelial dysfunction in PE.
INTRODUCTION: There is a consensus that factors released by the placenta to maternal circulation, including TNF-α, play a key role in activating the maternal endothelium in pregnancies with preeclampsia (PE). Dual perfusion preserves the structural organization of the placenta to a greater degree than other in vitro systems and has been used by our group and others to examine placental pathophysiology associated with PE. The objective of this study was to use the dual perfusion model to test whether TNF-α released by the placenta to maternal perfusate affects pro-inflammatory cytokine secretion by, and activation of, endothelial cells, thereby furthering our understanding of placental and endothelial dysfunction in PE. METHOD: We used maternal perfusate, two endothelial cell lines (HUVECs and HEECs), and a TNF-α blocking antibody to test whether placental-derived TNF-α plays a significant role in altering the expression and secretion of pro-inflammatory cytokines in endothelial cells as well as the expression of activation markers in this cell type. RESULTS: The presence of maternal perfusate significantly enhanced IL-6, IL-8, and MCP-1 secretion, levels of their mRNA, as well as mRNA levels of markers of endothelial activation (E-selectin, ICAM-1, and VCAM-1). The addition of a TNF-α blocking antibody significantly inhibited the maternal perfusate-mediated enhancement of cytokine secretion by, and expression of activation markers, in both HUVECs and HEECs. DISCUSSION: These results demonstrate that TNF-α significantly contributed to endothelial cell pro-inflammatory cytokine secretion and activation suggesting that blocking TNF-α action may mitigate the effects of maternal endothelial dysfunction in PE.
Authors: Hiten D Mistry; Melissa V Hott Ogalde; Fiona Broughton Pipkin; Geneviève Escher; Lesia O Kurlak Journal: Front Med (Lausanne) Date: 2020-06-12
Authors: Rohaina Che Man; Nadiah Sulaiman; Mohamad Fikeri Ishak; Ruszymah Bt Hj Idrus; Mohd Ramzisham Abdul Rahman; Muhammad Dain Yazid Journal: Int J Environ Res Public Health Date: 2020-10-26 Impact factor: 3.390