title: 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.
authors.affiliation: Intensive Care Unit, First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Intensive Care Unit, First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Zhenggang
authors.initials: Z
authors.lastname: Luan
authors.affiliation: Intensive Care Unit, First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Yingjian
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Intensive Care Unit, First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Yina
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Intensive Care Unit, First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Ma
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology / Q000473:pathology*; D000818:Animals; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D015536:Down-Regulation; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation; D053583:Interleukin-1beta / Q000032:analysis; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000201:enzymology / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000737:chemistry / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D024243:HMGB1 Protein; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D004247:DNA; D009195:Peroxidase