SFI Reduces the Nucleocytoplasmic Transportation of HMGB1 by Upregulating HDAC3 in LPS-induced RAW264.7 Cells

Abstract

Shenfu injection (SFI) is widely used for treating endotoxin shock in China. In the present study, to investigate the anti-inflammatory effects of SFI and further explored the potential mechanism of HMGB1 nuclear translocation, we established a vitro cell model provoked by lipopolysaccharide (LPS), observed nucleocytoplasmic translocation of high mobility group box 1 (HMGB1) and the relationship between histone deacetylase 3 (HDAC3) and HMGB1 under SFI intervention. The results showed that SFI upregulated the transcription and expression of HDAC3 in RAW264.7 cells, inhibited the nuclear to cytoplasmic translocation of HMGB1 and its subsequent extracellular release, and depressed the secretion of HMGB1, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). However, targeted knockdown of HDAC3 induced an increase in HMGB1 translocation to the cytoplasm, and HMGB1 localization was not altered significantly following LPS stimulation. SFI failed to reverse the abnormal localization of HMGB1. These results suggested that SFI may inhibit LPS-induced HMGB1 nuclear translocation in RAW264.7 cells through upregulating HDAC3 expression, thereby inhibiting its downstream pathway and suppressing inflammatory response.