The cytokine activity of HMGB1
Abstract
High mobility group box 1 (HMGB1) is a highly conserved, ubiquitous protein present in the nuclei and cytoplasm of nearly all cell types. We recently discovered that HMGB1 is secreted into the extracellular milieu and acts as a proinflammatory cytokine. Administration of HMGB1 to normal animals causes inflammatory responses, including fever, weight loss and anorexia, acute lung injury, epithelial barrier dysfunction, arthritis, and death. Anti-HMGB1 treatment, with antibodies or specific antagonists, rescues mice from lethal endotoxemia or sepsis and ameliorates the severity of collagen-induced arthritis and endotoxin-induced lung injury. Here, we give an abridged review of the cytokine activity of HMGB1, its secretion and release into the extracellular milieu, the putative signal transduction pathways, including interaction with cell-surface receptors and intracellular signaling, and its role in several inflammatory diseases. Finally, the therapeutic potential of blocking HMGB1 in the treatment of inflammatory diseases is discussed.
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Direct administration of HMGB-1 into the CNS activates NF-κB-dependent transcription, primes the NLRP3 inflammasome, and increases proinflammatory cytokines, including IL-1β.
“Indeed, direct administration of HMGB-1 into the CNS activates NF-κB-dependent transcription, primes the NLRP3 inflammasome, and increases proinflammatory cytokines, including IL-1β (O' Connor et al, 2003a;Yang et al, 2005;Xiang et al, 2011;Frank et al, 2015a).”
From Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal (2017) · cites this paper as Yang et al, 2005
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- Authors
- Yang, H., Wang, H., Czura, C. J., & Tracey, K. J.
- Affiliations
- Northwell Health (US)
- Corresponding author
- Yang, Huan
- Venue
- Journal of Leukocyte Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-02-25
- Volume
- 78
- Issue
- 1
- Pages
- 1-8
- ISSN
- 0741-5400 (ISSN-L)
- 1938-3673
- OpenAlex
- W2123949218
- Cited by
- 545
- References
- 75
- Citations by year
- 2026: 14 · 2025: 13 · 2024: 13 · 2023: 21 · 2022: 20 · 2021: 23 · 2020: 16 · 2019: 18 · 2018: 24 · 2017: 27 · 2016: 30 · 2015: 33 · 2014: 47 · 2013: 42 · 2012: 31
- FWCI
- 3.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Leukocyte Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- The North Shore-Long Island Jewish Health System (M01 RR018535)
- National Institutes of Health
- National Institute of General Medical Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › S100 Proteins and Annexins
- Keywords
- HMGB1, high mobility group box 1, inflammatory cytokines, endotoxemia, sepsis, acute lung injury, collagen-induced arthritis, epithelial barrier dysfunction, fever, signal transduction, inflammatory diseases, anti-inflammatory therapy
- MeSH terms
- Animals, Cell Communication, Disease Models, Animal, Humans, Inflammation, Signal Transduction, Cytokines, Cell Death, Sepsis, Inflammation Mediators, HMGB1 Protein
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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