Lipopolysaccharide induces BV2 microglial cell migration via a decrease in SET8 expression.

Excessively activated microglia exhibit increased migration, resulting in tissue damage and chronic inflammation. Src was confirmed to play an important role in regulation of cell motility following lipopolysaccharide (LPS) treatment. SET8 plays an important part in multiple cellular signal pathways. In this study, we speculated SET8 is involved in LPS-induced microglial migration via regulation of Src expression. Our study showed that LPS promoted cell migration via augment of Src expression in BV2 cells. Moreover, LPS treatment decreased SET8 expression and upregulated the expression of the transcription factor ETS proto-oncogene 1 (ETS1). Overexpression both SET8 and siETS1 reversed LPS-induced Src expression and cell migration. The effects of shSET8 and ETS1 overexpression do the same thing with those of LPS treatment. Decrease of Src expression reversed the shSET8-induced and ETS1 overexpression-induced migration of BV2 cells. Further, SET8 was observed to associate with ETS1. ChIP assay indicated H4K20me1, a downstream target of SET8, in addition to ETS1, was enriched at the Src promoter region. Furthermore, shSET8 increased Src promoter activity and also increased the positive effect of ETS1 overexpression on Src promoter activity. This study represents that SET8 associates with ETS1 to regulate Src expression, which is involved in LPS-induced BV2 cell migration.