1. Decidual NK cell-derived conditioned medium (dNK-CM) mediates VEGF-C secretion in extravillous cytotrophoblasts.
- Author
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Eastabrook GD, Hu Y, Tan R, Dutz JP, Maccalman CD, and von Dadelszen P
- Subjects
- Antibodies, Blocking, Cell Line, Female, Humans, Imidazoles pharmacology, Interferon-gamma immunology, Interferon-gamma pharmacology, Janus Kinases antagonists & inhibitors, Janus Kinases metabolism, Placenta metabolism, Placentation, Pregnancy, Pyridines pharmacology, RNA Interference, RNA, Small Interfering, Receptors, Interferon antagonists & inhibitors, Receptors, Interferon immunology, STAT1 Transcription Factor genetics, STAT1 Transcription Factor metabolism, p38 Mitogen-Activated Protein Kinases metabolism, Interferon gamma Receptor, Culture Media, Conditioned pharmacology, Decidua cytology, Killer Cells, Natural metabolism, Trophoblasts metabolism, Vascular Endothelial Growth Factor C metabolism
- Abstract
Problem: The regulatory mechanisms involved in VEGF-C secretion by trophoblasts during placentation are poorly understood. We investigated whether or not decidual natural killer cell conditioned medium (dNK-CM) stimulated VEGF-C secretion in the extravillous cytotrophoblast (EVT) cell line HTR8/SVneo., Method of Study: The effects of dNK-CM and recombinant IFN-γ on VEGF-C induction by HTR8/SVneo were studied in the absence or presence of IFN-γ or its receptor blocking antibodies, p38 inhibitor (SB202190), JAK inhibitor (JAK inhibitor-1, JI-1), and on STAT1 knockdown HTR8/SVneo. VEGF-C was quantified by ELISA. FACS was used to investigate the phosphorylations of Tyr701 or Ser727 of STAT1 on stimulated HTR8/SVneo., Results: dNK-CM facilitated VEGF-C secretion by HTR8/SVneo. IFN-γ and IFN-γR1 or IFN-γR2 blocking antibodies reduced both dNK-CM- and IFN-γ-induced VEGF-C secretion. Phosphorylations on Tyr701 or Ser727 of STAT1 were elevated upon stimulation. Secretion of VEGF-C was reduced by treatment with SB202190, JI-1, or STAT1 knockdown by siRNA., Conclusion: VEGF-C production by trophoblasts is regulated by soluble factors secreted by dNK through p38 and JAK-STAT1 pathways., (© 2011 John Wiley & Sons A/S.)
- Published
- 2012
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