Interleukin-27 Inhibits Trophoblast Cell Invasion and Migration by Affecting the Epithelial-Mesenchymal Transition in Preeclampsia.

Abstract

Preeclampsia (PE) is a pregnancy-specific disorder representing a major cause of maternal and perinatal morbidity and mortality. Invasive and migratory phenotypes are acquired by trophoblasts through the process of epithelial-mesenchymal transition (EMT). Studies have shown that trophoblast EMT events are dysregulated in PE and play an important role in its development. Dysregulation of interleukin (IL)-27 and IL-27R (T-cell cytokine receptor (TCCR)/WSX -1) is relevant to PE. In this study, our results demonstrated that IL-27 did not significantly affect the proliferation and apoptosis of HTR -8/SVneo trophoblast cells, while it did significantly inhibit trophoblast invasion and migration. The expression of EMT-related proteins in HTR-8/SVneo cells and extravillous explants was detected after treatment with IL-27. Expression of epithelial markers was increased, and mesenchymal marker expression was reduced. Furthermore, we found that IL-27 could induce significant phosphorylation of Signal Transducer and Activator of Transcription 1 (STAT1) and Signal Transducer and Activator of Transcription 3 (STAT3) in a time-dependent manner in HTR-8/SVneo cells. Selective inhibitors of STAT1 (STAT1 siRNA) and STAT3 (STAT3 siRNA) were used to determine whether both STAT1 and STAT3 are required for IL-27-mediated inhibition of EMT. STAT1 inhibition in IL-27-treated cells attenuated the IL-27 effect, while the inhibition of STAT3 activation had no effect on the development of the epithelial phenotype. These results demonstrate that IL-27 may inhibit trophoblast cell migration and invasion by affecting the EMT process through an STAT1-dominant pathway in PE.