Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, BC, Canada.
Am J Reprod Immunol. 2012 Feb;67(2):101-11. doi: 10.1111/j.1600-0897.2011.01075.x. Epub 2011 Oct 17.
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.
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.
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.
VEGF-C production by trophoblasts is regulated by soluble factors secreted by dNK through p38 and JAK-STAT1 pathways.
滋养层细胞在胎盘形成过程中分泌 VEGF-C 的调节机制尚不清楚。我们研究了蜕膜自然杀伤细胞条件培养基（dNK-CM）是否刺激绒毛外滋养层（EVT）细胞系 HTR8/SVneo 分泌 VEGF-C。
研究了 dNK-CM 和重组 IFN-γ 在不存在或存在 IFN-γ 或其受体阻断抗体、p38 抑制剂（SB202190）、JAK 抑制剂（JAK 抑制剂-1，JI-1）的情况下对 HTR8/SVneo 诱导 VEGF-C 的影响，以及 STAT1 敲低 HTR8/SVneo。通过 ELISA 定量 VEGF-C。使用 FACS 研究刺激 HTR8/SVneo 上 STAT1 的 Tyr701 或 Ser727 的磷酸化。
dNK-CM 促进 HTR8/SVneo 分泌 VEGF-C。IFN-γ 和 IFN-γR1 或 IFN-γR2 阻断抗体减少了 dNK-CM 和 IFN-γ 诱导的 VEGF-C 分泌。STAT1 的 Tyr701 或 Ser727 磷酸化在刺激后升高。用 SB202190、JI-1 或 siRNA 敲低 STAT1 处理后，VEGF-C 的分泌减少。
滋养层细胞的 VEGF-C 产生受 dNK 通过 p38 和 JAK-STAT1 途径分泌的可溶性因子调节。
