IL-27 Affects The Function Of Trophoblast Cells And Vascular Endothelial Cells And Participates In The Related Mechanism Research Of Preeclampsia

Objectives: IL-27 induces a proinflammatory cytokine profile in trophoblast cells and plays an important role in preeclampsia(PE).The effects of IL-27 on trophoblast functions remains unclear.We investigated whether IL-27 affects trophoblast functions and the related signaling pathways.Method: The effects of IL-27 on HTR-8/SVneo cell functions and the outgrowth of extravillous explants were investigated.The expression of epithelial-mesenchymal transition(EMT)markers in HTR-8/SVneo cells and extravillous explants was also detected after treatment with IL-27 via western blotting and immunofluorescence.Selective inhibitors of STAT1(STAT1 si RNA)and STAT3(STAT3 si RNA)were used to determine whether both STAT1 and STAT3 are required for IL-27 mediated inhibition of EMT.Results: IL-27 did not significantly affect the proliferation and apoptosis of HTR-8/SVneo trophoblast cells,while it did significantlyinhibit trophoblast invasion and migration.Expression of epithelial markers was increased and mesenchymal marker expression was reduced.IL-27 induced significant phosphorylation of STAT1 and STAT3 in a time dependent manner in HTR-8/SVneo cells.STAT1 inhibition in IL-27-treated cells reversed the IL-27 effect.Conclusion: IL-27 inhibits trophoblast cell invasion and migration by affecting the EMT process through a STAT1 dominant pathway in PE.Objective : To explore the mechanism of IL-27 involved in the pathogenesis of preeclampsia(PE).Methods:(1)Western blot was used to detect the expression of IL-27 and its receptor WSX-1 in placentas.(2)Isolation and culture of primary human umbilical vein endothelial cells(HUVECs)were conducted,and the cells were identified by immunofluorescence.(3)The primary HUVECs were treated with IL-27(50 ng/m L)at time points from 0.25 to 2 hours and analyzed for activated or tyrosine phosphorylated JAK2(p-JAK2)and STAT1(p-STAT1)proteins by Western blot.(4)Cell treatments of each group were as follows: normal culture group(Con),DMSO culture group,JAK2 inhibitor AG490 culture group(AG490),IL-27 culture group,DMSO + IL-27 culture group,AG490 + IL-27 culture group.The tube formation assays were used to detect the effects of IL-27 on the tube formation capacity of primary HUVECs.Results:(1)IL-27 and WSX-1 protein level were both increased in the PE group compared to the control group.(2)Primary HUVECs were successfully isolated and cultured.(3)After exposure to IL-27,we found that the JAK2/STAT1 pathway is activated in primary HUVECs.(4)The migration and tube formation abilities of IL-27 group and DMSO + IL-27 group were significantly reduced.There were no significantly differences between AG490 group and AG490 + IL-27 group.Conclusion:These results suggest that IL-27 may play a critical role in the pathogenesis of PE through JAK2/STAT1 pathway.