Tandem Mass Tag-Based Proteomics Analysis Reveals the Mechanism Underlying the Interleukin-6-Mediated Regulation of Trophoblast Function in Preeclampsia

Objective: we investigate the mechanism whereby interleukin-6 (IL-6), an important inflammatory marker, influences trophoblast function during preeclampsia. Methods: Quantitative PCR and enzyme-linked immunosorbent assay were used to determine the IL-6 mRNA and protein levels, respectively. CCK8 and transwell assays were used to detect how IL-6 affects the proliferation and invasion abilities, respectively, of HTR-8/SVneo cells; the tube-forming assay was used to detect how IL-6 affects the angiogenesis ability of human umbilical vein endothelial cells (HUVECs) after their co-culture with HTR-8/SVneo cells. Using tandem mass tag-based proteomics analysis, we screened for different proteins before and after IL-6 stimulation; Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to explore the functions and signal pathways associated with, these proteins. Results: The IL-6 levels were higher in the placenta of preeclampsia group than in normal group. IL-6 suppressed the proliferation and invasion of HTR-8/SVneo cells, but promoted the angiogenesis of HUVECs. Seventy differentially expressed IL-6 downstream proteins were identified; these were enriched with various biological processes, molecular functions, cellular components, and biological pathways. Conclusions: IL-6 regulates trophoblast function by interacting with multiple proteins and pathways. Proteomics-based screening represents a macroscopic means for elucidating the molecular mechanisms underlying preeclampsia.