Open AccessDownregulation of high mobility group box 1 attenuates the severity of acute lung injury in endotoxemic mice
Author(s) -
Xiaojuan Zhang,
Zhenggang Luan,
Yingjian Liang,
Yina Liu,
Xiaochun Ma
Publication year - 2015
Publication title -
molecular medicine reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.727
H-Index - 56
eISSN - 1791-3004
pISSN - 1791-2997
DOI - 10.3892/mmr.2015.3251
Subject(s) - hmgb1 , downregulation and upregulation , tumor necrosis factor alpha , lipopolysaccharide , sepsis , malondialdehyde , inflammation , small interfering rna , lung , medicine , oncogene , myeloperoxidase , interleukin 6 , immunology , cytokine , chemistry , biology , cell cycle , oxidative stress , cell culture , cancer , transfection , biochemistry , genetics , gene
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.