Downregulation of high mobility group box 1 attenuates the severity of acute lung injury in endotoxemic mice

Abstract

High mobility group box 1 (HMGB1) is a systemic inflammation-associated cytokine mediator. The aim of the present study was to examine the effect of the downregulation of HMGB1 in a lipopolysaccharide (LPS)-induced mouse model of acute lung injury (ALI). It was identified that serum levels of tumor necrosis factor-α and interleukin-1β, lung myeloperoxidase activity and malondialdehyde content, as well as lung wet/dry weight ratios were all increased following LPS challenge. However, LPS-mediated increases in these parameters were significantly downregulated in HMGB1 small interfering (si)RNA-treated mice versus the negative control siRNA-treated mice. In addition, the administration of HMGB1 siRNA in LPS-treated mice resulted in a decreased DNA binding activity of nuclear factor-κB (NF-κB) in the lung. It was demonstrated that downregulation of HMGB1 decreases inflammation and the severity of sepsis associated with ALI, possibly via inhibiting the NF-κB DNA-binding activity. The present data support HMGB1 as a contributor to the pathogenesis of LPS-induced sepsis and ALI.