Secretion of tumor necrosis factor-alpha from human placental tissues induced by hypoxia-reoxygenation causes endothelial cell activation in vitro: a potential mediator of the inflammatory response in preeclampsia.
Preeclampsia is a hypertensive complication of human pregnancy characterized by generalized maternal endothelial cell activation. Circulating pro-inflammatory cytokines derived from the placenta are thought to play a key role. We recently demonstrated that hypoxia-reoxygenation (H/R) of placental tissues in vitro causes equivalent oxidative stress to that seen in preeclampsia. Our aim was to determine whether H/R also increases production of tumor necrosis factor-alpha (TNF-alpha), and whether conditioned media from samples exposed to H/R causes activation of human umbilical vein endothelial cells (HUVECs). Concentrations of mRNA encoding TNF-alpha were significantly higher in placental tissues subjected to H/R compared to hypoxic or normoxic controls. Although there was no difference in the concentrations of TNF-alpha protein in tissue homogenates, levels of TNF-alpha protein in the medium were significantly higher after H/R compared to controls, indicating increased secretion. Furthermore, conditioned medium from samples subjected to H/R caused increased expression of E-selectin by HUVECs, and the addition of anti-TNF-alpha antibodies significantly reduced that activation. These results are consistent with our hypothesis that intermittent perfusion of the placenta, secondary to reduced trophoblast invasion, causes increased secretion of TNF-alpha, and that this contributes to the activation of maternal endothelial cells that characterizes preeclampsia.
Department of Obstetrics and Gynaecology, Chang Gung Memorial Hospital, Taipei, Taiwan.
Tai-Ho
TH
Hung
D Stephen
DS
Charnock-Jones
Jeremy N
JN
Skepper
Graham J
GJ
Burton
D051722:ADAM Proteins; D000072198:ADAM17 Protein; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D019040:E-Selectin / Q000096:biosynthesis / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007249:Inflammation / Q000276:immunology; D008666:Metalloendopeptidases / Q000378:metabolism; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D011247:Pregnancy; D015427:Reperfusion Injury / Q000503:physiopathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology
D017077:Culture Media, Conditioned; D019040:E-Selectin; D014409:Tumor Necrosis Factor-alpha; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000072198:ADAM17 Protein