Cited by 4,221Advanced Glycation End Products researchImmune Response and InflammationCell death mechanisms and regulation

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Release of chromatin protein HMGB1 by necrotic cells triggers inflammation

Scaffidi, Paola, Misteli, Tom, Bianchi, Marco E.·2002·Nature

DOI 10.1038/nature00858

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Abstract

High mobility group 1 (HMGB1) protein is both a nuclear factor and a secreted protein. In the cell nucleus it acts as an architectural chromatin-binding factor that bends DNA and promotes protein assembly on specific DNA targets. Outside the cell, it binds with high affinity to RAGE (the receptor for advanced glycation end products) and is a potent mediator of inflammation. HMGB1 is secreted by activated monocytes and macrophages, and is passively released by necrotic or damaged cells. Here we report that Hmgb1(-/-) necrotic cells have a greatly reduced ability to promote inflammation, which proves that the release of HMGB1 can signal the demise of a cell to its neighbours. Apoptotic cells do not release HMGB1 even after undergoing secondary necrosis and partial autolysis, and thus fail to promote inflammation even if not cleared promptly by phagocytic cells. In apoptotic cells, HMGB1 is bound firmly to chromatin because of generalized underacetylation of histone and is released in the extracellular medium (promoting inflammation) if chromatin deacetylation is prevented. Thus, cells undergoing apoptosis are programmed to withhold the signal that is broadcast by cells that have been damaged or killed by trauma.

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“-host disease; HMGB1, High mobility group box 1; HUS, Hemolytic uremic syndrome; IRI, Ischemiareperfusion injury; LPS, Lipopolysaccharide; Mac-1, Macrophage-1 antigen; MPA, Microscopic polyangiitis; MPO, Myeloperoxidase; NETs, Neutrophil extracellular traps; NF-κB, Nuclear factor-kappa B; RAGE, Receptor for advanced g…”
BackgroundInfluential
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Background
Inhibitor of NF-κB Kinases α and β Are Both Essential for High Mobility Group Box 1-Mediated Chemotaxis
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Self-citation
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Background
Receptor for Advanced Glycation End Products Expression on T Cells Contributes to Antigen-Specific Cellular Expansion In Vivo
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BackgroundInfluential
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Authors: Scaffidi, P., Misteli, T., & Bianchi, M. E.
Affiliations: National Institutes of Health (US)
Vita-Salute San Raffaele University (IT)
Corresponding author: Bianchi, Marco E.
ORCID: Scaffidi, Paola
Misteli, Tom
Bianchi, Marco E.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2002-07-11
Volume: 418
Issue: 6894
Pages: 191-195
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature00858
OpenAlex: W2004266769
Cited by: 4,221
References: 26
Citations by year: 2026: 104 · 2025: 106 · 2024: 129 · 2023: 158 · 2022: 168 · 2021: 233 · 2020: 204 · 2019: 196 · 2018: 211 · 2017: 205 · 2016: 228 · 2015: 253 · 2014: 276 · 2013: 261 · 2012: 230
FWCI: 47.06
Type: journal article
Language: en
Update notices: erratum (2010-09-30)
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
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 › Cell death mechanisms and regulation
Keywords: HMGB1, necrosis, apoptosis, inflammation, chromatin, histone acetylation, RAGE, extracellular HMGB1 release, secondary necrosis, phagocytosis, damage-associated molecular patterns
MeSH terms: Acetylation, Animals, Cell Survival, Chromatin, HeLa Cells, Humans, Inflammation, Necrosis, Protein Binding, Apoptosis, Gene Deletion, HMGB1 Protein, Rats

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Release of chromatin protein HMGB1 by necrotic cells triggers inflammation

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