HuR induces inflammatory responses in HUVECs and murine sepsis via binding to HMGB1

The aim of the present study was to explore the roles of human antigen R (HuR) in sepsis. Reverse transcription-quantitative polymerase chain reaction and western blot analyses demonstrated that overexpression of HuR increased the expression of high-mobility group box 1 (HMGB1) in human umbilical vein endothelial cells (HUVECs). HMGB1 was investigated as a potential target of HuR through bioinformatics and RNA-immunoprecipitation assays. Furthermore, treatment with HuR small interfering (si)RNA suppressed the lipopolysaccharide (LPS)-mediated release of HMGB1 and reduced HMGB1-mediated hyperpermeability and leukocyte migration in HUVECs and in septic mice. In addition, HuR-siRNA injection reduced cecal ligation and puncture (CLP)-induced HMGB1 release, reduced production of interleukin 6 and lowered mortality rates. Notably, the promotive effects of HuR overexpression on the inflammatory response were attenuated when HUVECs were co-treated with HMGB1 short hairpin RNA. Therefore, the present results indicated that the ectopic expression of HuR may induce inflammatory responses and thus sepsis by activating the HMGB1 signaling pathway.