Downregulation of high mobility group box 1 attenuates the severity of acute lung injury in endotoxemic mice
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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.
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The downregulation of HMGB1 in hypoxia may signify cytoprotection from cellular damage, such as production of reactive oxygen species, as seen in normoxia cultures.
“Therefore, its downregulation in hypoxia may signify cytoprotection from cellular damage, such as production of reactive oxygen species, as seen in normoxia cultures [61, 62].”
From Short-term physiological hypoxia potentiates the therapeutic function of mesenchymal stem cells (2018) · cites this paper as [62]
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References 31 · Cited by 8
- Authors
- ZHANG, X., LUAN, Z., LIANG, Y., LIU, Y., & MA, X.
- Affiliations
- First Hospital of China Medical University (CN)
- Venue
- Molecular Medicine Reports
- Publisher
- Spandidos Publications
- Published
- 2015-01-26
- Volume
- 11
- Issue
- 6
- Pages
- 4513-4517
- ISSN
- 1791-2997 (ISSN-L)
- 1791-3004
- OpenAlex
- W2035850128
- Cited by
- 8
- References
- 31
- Citations by year
- 2024: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2018: 1 · 2016: 1 · 2015: 1
- FWCI
- 0.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Medicine Reports (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
- Keywords
- HMGB1, acute lung injury, lipopolysaccharide, sepsis, NF-kappaB DNA binding, siRNA knockdown, inflammation, TNF-α, IL-1β, myeloperoxidase, malondialdehyde, oxidative stress, endotoxemia
- MeSH terms
- Animals, DNA, Enzyme-Linked Immunosorbent Assay, Inflammation, Lipopolysaccharides, Lung, Malondialdehyde, Mice, Inbred C57BL, Peroxidase, Protein Binding, Severity of Illness Index, Tumor Necrosis Factor-alpha, Down-Regulation, NF-kappa B, Electrophoretic Mobility Shift Assay, HMGB1 Protein, RNA Interference, RNA, Small Interfering, Mice, Interleukin-1beta, Acute Lung Injury
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