Interleukin-1 beta signals through the ERK signalling pathway to modulate human placental trophoblast migration and invasion in the first trimester of pregnancy

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Discussion: This study demonstrated IL-1β expression in placenta and decidua, and that it regulates EVT invasion and migration.

Keywords: ERK; IL-1β; Invasion; Migration; Trophoblast.