Sodium dichloroacetate improves migration ability by suppressing LPS-induced inflammation in HTR-۸/SVneo cells via the TLR۴/NF-κB pathway

Objective(s): Inadequate cytotrophoblast migration and invasion are speculated to result in preeclampsia, which is a pro-inflammatory condition. Sodium dichloroacetate (DCA) exerts anti-inflammatory actions. Thus,we sought to investigate the effect of DCA on the migration function of the lipopolysaccharide (LPS)-stimulated human-trophoblast-derived cell line (HTR-۸/SVneo).Materials and Methods: HTR-۸/SVneo cells were treated with LPS to suppress cell migration. Cell migration was examined by both scratch wound healing assay and transwell migration assay. Western blotting was used to analyze the expression levels of toll-like receptor-۴ (TLR۴), nuclear factor-κB (NF-κB), TNF-α, IL-۱β, and IL-۶ in the cells.Results: DCA reversed LPS-induced inhibition of migration in HTR-۸/SVneo cells. Furthermore, DCA significantly suppressed LPS-induced activation of TLR۴, phosphorylation of NF-κB (p۶۵), translocation of p۶۵ into the nucleus, and the production of pro-inflammatory cytokines (TNF-α, IL-۱β, and IL-۶). Treatment with inhibitors of TLR۴ signal transduction (CLI۰۹۵ or MD۲-TLR-۴-IN-۱) reduced LPS-induced overexpression of pro-inflammatory cytokines, and a synergistic effect was found between TLR۴ inhibitors and DCA in HTR-۸/SVneo cells. Conclusion: DCA improved trophoblast cell migration function by suppressing LPS-induced inflammation, at least in part, via the TLR۴/NF-κB signaling pathway. This result indicates that DCA might be a potential therapeutic candidate for human pregnancy-related complications associated with trophoblast disorder.

کلیدواژه ها:

HTR-۸/SVneo cells ، Inflammation ، Migration ، Sodium dichloroacetate ، Toll-like receptor-۴