title: Decidual NK cell-derived conditioned medium (dNK-CM) mediates VEGF-C secretion in extravillous cytotrophoblasts.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  VEGF-C production by trophoblasts is regulated by soluble factors secreted by dNK through p38 and JAK-STAT1 pathways.
authors: Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, BC, Canada. geastabrook@cw.bc.ca
authors: Genevieve D M
authors: GD
authors: Eastabrook
authors: Yuxiang
authors: Y
authors: Hu
authors: Rusung
authors: R
authors: Tan
authors: Jan P
authors: JP
authors: Dutz
authors: Colin D
authors: CD
authors: Maccalman
authors: Peter
authors: P
authors: von Dadelszen
mesh_terms: D019138:Antibodies, Blocking; D002460:Cell Line; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D003656:Decidua / Q000166:cytology*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology; D053612:Janus Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D007694:Killer Cells, Natural / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism; D010929:Placentation; D011247:Pregnancy; D011725:Pyridines / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering; D017471:Receptors, Interferon / Q000037:antagonists & inhibitors / Q000276:immunology; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D014327:Trophoblasts / Q000378:metabolism*; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000096743:Interferon gamma Receptor
chemical_list: D019138:Antibodies, Blocking; D017077:Culture Media, Conditioned; D007093:Imidazoles; D007371:Interferon-gamma; D053612:Janus Kinases; D011725:Pyridines; D034741:RNA, Small Interfering; D017471:Receptors, Interferon; D050794:STAT1 Transcription Factor; D042582:Vascular Endothelial Growth Factor C; D048051:p38 Mitogen-Activated Protein Kinases; D000096743:Interferon gamma Receptor; C494079:STAT1 protein, human; C467486:VEGFC protein, human; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole