Sevoflurane inhibited inflammatory response induced by TNF-α in human trophoblastic cells through p38MAPK signaling pathway.

Purpose: Excessive inflammatory response is one of the possible pathogenic mechanisms of preeclampsia (PE). It remains unclear whether sevoflurane has an anti-inflammatory effect in human trophoblastic cells, which are corresponding to the dysfunction of placentas in PE. This study probed into the regulatory function of sevoflurane toward HTR8/SVneo cells so as to find PE pathology and PE treatment.Materials and methods: HTR8/SVneo cells were treated with sevoflurane, TNF-α with different concentrations, sevoflurane plus 10 ng/mL TNF-α and SB203580 plus 10 ng/mL TNF-α. Cell counting kit-8 (CCK-8) assays were performed to detect cell viability, while enzyme linked immunoSorbent assay (ELISA) was used to measure IL-6, IL-8, GM-CSF and MCP-1 levels in HTR8/SVneo cells. Besides, relative mRNA expression levels of IL-6 and IL-8 were tested via quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), and p38 phosphorylation-related protein expressions were assessed through western blot.Results: Cell viability remained stable when HTR8/SVneo cells were treated with or without sevoflurane and SB203580 in inflammatory microenvironment created by TNF-α. MCP-1 and GM-CSF levels, as well as gene expressions of IL-6 and IL-8 in HTR8/SVneo cells were greatly increased by TNF-α (5, 10 and 20 ng/mL), but reversed by sevoflurane and SB203580. Simultaneously, TNF-α-induced phosphorylation of p38MAPK signaling pathway was inhibited by sevoflurane and SB203580.Conclusions: Sevoflurane inhibited inflammatory response induced by TNF-α in human trophoblastic cells HTR8/SVneo through suppressing the phosphorylation of p38MAPK signaling pathway.

Sevoflurane induces apoptosis of isolated placental trophoblast cells and stimulates expressions of TNF-α and IL-6.

Studies have shown that narcotic drugs may affect the function of placental trophoblast cells. The aim of this study was to investigate the effect of sevoflurane on apoptosis and proinflammatory cytokines in isolated placental trophoblast cells. The primary placental trophoblast cells were obtained from a total of 20 parturients, which were randomly divided into 4 groups and treated with 3% sevoflurane for 0 minutes (S0), 15 minutes (S15), 30 minutes (S30) and 60 minutes (S60). The expressions of CK7 and vimentin were detected by immunofluorescence. The apoptosis of trophoblast cells was tested by TUNEL assay. The concentrations and protein expressions of TNF-α and IL-6 were determined by ELISA and Western-blot. The apoptosis number and apoptosis rate of placental trophoblast cells in S60 and S30 groups were higher than that in S15 and S0 groups (P<0.05). The concentrations of TNF-α and IL-6 in cell culture medium of S60 and S30 groups were elevated as compared to S15 and S0 groups (P<0.05). Compared with S15 and S0 groups, the protein expressions of TNF-α and IL-6 in placental trophoblast cells of S60 and S30 groups also showed an significant increase (P<0.05). Moreover, the expressions of TNF-α and IL-6 were positively correlated with the apoptosis of cytotrophoblast cells. Using for a long time of sevoflurane induces the apoptosis of placental trophoblast cells and increases the expressions of pro-inflammatory factors, suggesting that the duration of sevoflurane anesthesia should be controlled within 15 minutes.