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

作者：Zhang, Xiaojuan; Luan, Zhenggang; Liang, Yingjian; Liu, Yina; Ma, Xiaochun^*

来源：Molecular Medicine Reports, 2015, 11(6): 4513-4517.

DOI：10.3892/mmr.2015.3251

• acute lung injury
• high mobility group box 1
• inflammation
• small interfering RNA
• nuclear factor-kappa B

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 (ALT). It was identified that serum levels of tumor necrosis factor-alpha and interleukin-1 beta, 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-kappa B (NF-kappa B) 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-kappa B DNA-binding activity. The preSent data support HMGB1 as a contributor to the pathogenesis of LPS-induced sepsis and ALT.

• 出版日期2015-6
• 单位中国医科大学