Extracellular release of HMGB1 in lipopolysaccharide-induced hepatocytes and its signaling pathway

Objective To study the extracellular release of high mobility group box 1(HMGB1) in hepatocytes induced by lipopolysaccharide and its intracellular signaling pathway.Methods The changes of HMGB1 mRNA expression and HMGB1 concentration in the culture medium were investigated after BRL-3A hepatocytes were induced with 100 μg/L lipopolysaccharide for 6-24 hours.The effects of MAPKs pathway inhibitors(SB202190 and U0126) with various concentrations were observed on HMGB1 mRNA expression and extracellular release in lipopolysaccharide-induced BRL-3A hepatocytes.HMGB1 concentration was determined by enzyme-linked immunosorbent assay(ELISA).Results The level of HMGB1 mRNA expression and HMGB1 concentration in the culture medium significantly increased after BRL-3A hepatocytes were induced by lipopolysaccharide for 6 hours(P0.01).The HMGB1 concentration continued to increase as the induction time lengthened.20 μmol/L SB202190 and 20 μmol/L U0126 partly inhibited extracellular release of HMGB1 in lipopolysaccharide-induced BRL-3A hepatocytes.But no effects were observed on HMGB1 mRNA expression for these inhibitors.Conclusion Lipopolysaccharide induces hepatocytes to release HMGB1,which mechanism is involved with intracellular MAPKs signaling pathway.