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Inflammatory processes are specifically enhanced in endothelial cells by placental-derived TNF-α : Implications in preeclampsia (PE)

Shaw, Jeff; Tang, Zhonghua; Schneider, Henning; Saljé, Karen; Hansson, Stefan R. LU and Guller, Seth (2016) In Placenta 43. p.1-8
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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Endothelium, Inflammation, Placental secretion, Preeclampsia, TNF-α
in
Placenta
volume
43
pages
8 pages
publisher
W B Saunders
external identifiers
  • Scopus:84964510310
ISSN
0143-4004
DOI
10.1016/j.placenta.2016.04.015
language
English
LU publication?
yes
id
4b1a37e0-1f85-4b33-9e07-fbb6df7b9825
date added to LUP
2016-05-31 13:06:05
date last changed
2016-11-21 11:51:10
@misc{4b1a37e0-1f85-4b33-9e07-fbb6df7b9825,
  abstract     = {<p>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.</p>},
  author       = {Shaw, Jeff and Tang, Zhonghua and Schneider, Henning and Saljé, Karen and Hansson, Stefan R. and Guller, Seth},
  issn         = {0143-4004},
  keyword      = {Endothelium,Inflammation,Placental secretion,Preeclampsia,TNF-α},
  language     = {eng},
  month        = {07},
  pages        = {1--8},
  publisher    = {ARRAY(0xb41b438)},
  series       = {Placenta},
  title        = {Inflammatory processes are specifically enhanced in endothelial cells by placental-derived TNF-α : Implications in preeclampsia (PE)},
  url          = {http://dx.doi.org/10.1016/j.placenta.2016.04.015},
  volume       = {43},
  year         = {2016},
}