Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510623, PR China.
Cancer Research Institute, Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, 510623, PR China.
Placenta. 2024 Jun;151:67-78. doi: 10.1016/j.placenta.2024.04.010. Epub 2024 Apr 26.
Interleukin-1 beta (IL-1β) can promote cell migration, invasion and metastasis in various cancer cells. The mechanism of its role in human trophoblast has not been fully investigated. Therefore, we aimed to investigate the expression level of IL-1β in first trimester decidua and placenta and its potential role in regulation of extravillous trophoblast cell (EVT) invasion and migration.
First trimester placenta and decidua were collected to study the expression levels of IL-1β and its receptors by immunohistochemical staining. Primary isolates of first trimester EVT or the HTR-8/SVneo trophoblast like cell line were used to assess migration and invasion. Matrix metalloproteinase levels were assessed by gelatin zymography and ELISA. The phosphorylation profile of signaling pathway proteins was detected with the Proteome Profiler Human Phospho-Kinase Array Kit. Differentially expressed proteins in cells was detected and verified by Western Blot.
IL-1β, its receptors and antagonist are expressed in first trimester placenta and decidua, exogenous IL-1β stimulates trophoblast cell outgrowth, migration and invasion through the ERK signaling pathway. IL-1β was significantly increased in the placenta at 6-7 weeks gestation compared with 8-9 weeks gestation (P < 0.0001). Transwell and RTCA assays indicated that IL-1β stimulates the invasion and migration of EVT. In addition, IL-1β promoted the phosphorylation of ERK 1/2. It also promoted the expression of MMP2 and MMP9 in EVT as demonstrated by gelatin zymography assay and enzyme linked immunosorbent assay.
This study demonstrated IL-1β expression in placenta and decidua, and that it regulates EVT invasion and migration.
白细胞介素-1β（IL-1β）可以促进多种癌细胞的迁移、侵袭和转移。其在人滋养层中的作用机制尚未完全研究清楚。因此，我们旨在研究 IL-1β在早孕期蜕膜和胎盘组织中的表达水平及其在调节绒毛外滋养细胞（EVT）侵袭和迁移中的潜在作用。
收集早孕期胎盘和蜕膜组织，通过免疫组织化学染色研究 IL-1β及其受体的表达水平。采用原代分离的早孕期 EVT 或 HTR-8/SVneo 滋养层样细胞系评估迁移和侵袭。通过明胶酶谱和 ELISA 评估基质金属蛋白酶水平。采用 Proteome Profiler Human Phospho-Kinase Array Kit 检测信号通路蛋白的磷酸化谱。通过 Western Blot 检测和验证细胞中差异表达的蛋白。
IL-1β、其受体和拮抗剂在早孕期胎盘和蜕膜中表达，外源性 IL-1β通过 ERK 信号通路刺激滋养层细胞的生长、迁移和侵袭。与 8-9 孕周妊娠相比，6-7 孕周妊娠胎盘组织中 IL-1β显著增加（P<0.0001）。Transwell 和 RTCA 实验表明，IL-1β刺激 EVT 的侵袭和迁移。此外，IL-1β促进 ERK 1/2 的磷酸化。通过明胶酶谱和酶联免疫吸附试验也证明，IL-1β促进 EVT 中 MMP2 和 MMP9 的表达。
本研究表明 IL-1β在胎盘和蜕膜中表达，并调节 EVT 的侵袭和迁移。
