Kato Erina, Yamamoto Tatsuo, Chishima Fumihisa
Department of Obstetrics and Gynecology, Nihon University School of Medicine, Tokyo, Japan.
Gynecol Obstet Invest. 2017;82(1):39-46. doi: 10.1159/000446279. Epub 2016 May 10.
Cytokines such as tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) play an important role in maintaining pregnancy. Toll-like receptors (TLRs) have also been associated with innate immune responses during pregnancy. Placenta growth factor (PlGF) is one of the angiogenic factors and soluble vascular endothelial growth factor receptor 1 (sVEGFR1) is one of the antiangiogenic factors that regulate PlGF function. To elucidate the effects of cytokines and TLR ligands on the production of angiogenic and antiangiogenic factors in trophoblasts, we examined the production of PlGF and sVEGFR1 from trophoblasts following stimulation with cytokines and TLR ligands.
Villous tissues were obtained from healthy pregnant women who had had an artificial abortion. The trophoblasts were isolated from villous tissues. Subsequently, trophoblasts were treated with TNF-α, IFN-γ and TLR ligands. The levels of PlGF and sVEGFR1 were measured by enzyme-linked immunosorbent assay. The expression of those mRNA was analyzed using quantitative reverse transcription PCR.
The production of PlGF in trophoblasts increased by the addition of TNF-α or IFN-γ and decreased by TLR4 ligand. sVEGFR1 levels also increased by following the stimulation with IFN-γ or TLR ligand.
Cytokines such as TNF-α and IFN-γ and TLR ligands may contribute to the production of angiogenic and antiangiogenic factors and may affect the placental formation.
肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）等细胞因子在维持妊娠中发挥重要作用。Toll样受体（TLR）也与妊娠期间的天然免疫反应有关。胎盘生长因子（PlGF）是血管生成因子之一，可溶性血管内皮生长因子受体1（sVEGFR1）是调节PlGF功能的抗血管生成因子之一。为了阐明细胞因子和TLR配体对滋养层细胞中血管生成和抗血管生成因子产生的影响，我们检测了细胞因子和TLR配体刺激后滋养层细胞中PlGF和sVEGFR1的产生情况。
从接受人工流产的健康孕妇中获取绒毛组织。从绒毛组织中分离出滋养层细胞。随后，用TNF-α、IFN-γ和TLR配体处理滋养层细胞。通过酶联免疫吸附测定法测量PlGF和sVEGFR1的水平。使用定量逆转录PCR分析这些mRNA的表达。
添加TNF-α或IFN-γ可使滋养层细胞中PlGF的产生增加，而TLR4配体可使其减少。IFN-γ或TLR配体刺激后，sVEGFR1水平也会增加。
TNF-α和IFN-γ等细胞因子以及TLR配体可能有助于血管生成和抗血管生成因子的产生，并可能影响胎盘形成。
