We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Tumor Necrosis Factor-α Inhibits Trophoblast Migration through Elevation of Plasminogen Activator Inhibitor-1 in First-Trimester Villous Explant Cultures.
- Authors
BAUER, SANDRA; POLLHEIMER, JÜRGEN; HARTMANN, JOHANNES; HUSSLEIN, PETER; APLIN, JOHN D.; KNÖFLER, MARTIN
- Abstract
We have tested the hypothesis that elevated concentrations of TNFα could impair trophoblast invasion. Using first-trimester placental explant cultures, we have demonstrated that the cytokine inhibits in vitro migration of extravillous trophoblasts (EVT) on collagen I, and invasion through Matrigel. To elucidate the underlying mechanism, proliferation and differentiation of EVT in vitro were analyzed by immunohistochemistry of serial sections, Western blotting, zymography, ELISA, and RT-PCR from RNA pools of mechanically separated cell populations. At 24 h of cultivation in the presence or absence of TNFα, anchorage and proliferation of trophoblasts had occurred to generate cell columns containing viable, post-mitotic, differentiated EVT [positive for integrins α1 and α5, matrix metalloproteinase (MMP)-2, and human leukocyte antigen-G1; negative for proliferating cellular nuclear antigen, cytokeratin 18 neoepitope, and in 5-Bromo-2-deoxy-uridine labeling]. At 72 h, control cells had broken away from the column to migrate through the extracellular matrix; whereas, in contrast, TNFα-treated EVT remained as contiguous cell columns, despite increased MMP-9 expression. Thus, in vitro MMP9 activity appears not to be essential for trophoblast migration. Expression of plasminogen activator inhibitor (PAI)-1 was elevated in TNFα-treated EVT, and adding antibodies that inhibit PAI-1 activity restored migration, whereas tissue-inhibitor-of-metalloproteinases-1-blocking antibodies were ineffective. Induction of PAI-1 by TNFα could be related to restricted trophoblast invasion in preeclampsia.
- Publication
Journal of Clinical Endocrinology & Metabolism, 2004, Vol 89, Issue 2, p812
- ISSN
0021-972X
- Publication type
Article
- DOI
10.1210/jc.2003-031351