Cited by 1,437Advanced Glycation End Products researchImmune Response and InflammationInflammasome and immune disorders

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HMGB1 Is a Therapeutic Target for Sterile Inflammation and Infection

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Andersson, Ulf, Tracey, Kevin J.·2011·Annual Review of Immunology

DOI 10.1146/annurev-immunol-030409-101323PMC PMC4536551

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Abstract

A key question in immunology concerns how sterile injury activates innate immunity to mediate damaging inflammation in the absence of foreign invaders. The discovery that HMGB1, a ubiquitous nuclear protein, mediates the activation of innate immune responses led directly to the understanding that HMGB1 plays a critical role at the intersection of the host inflammatory response to sterile and infectious threat. HMGB1 is actively released by stimulation of the innate immune system with exogenous pathogen-derived molecules and is passively released by ischemia or cell injury in the absence of invasion. Established molecular mechanisms of HMGB1 binding and signaling through TLR4 reveal signaling pathways that mediate cytokine release and tissue damage. Experimental strategies that selectively target HMGB1 and TLR4 effectively reverse and prevent activation of innate immunity and significantly attenuate damage in diverse models of sterile and infection-induced threat.

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Authors: Andersson, U., & Tracey, K. J.
Affiliations: Karolinska University Hospital (SE)
Feinstein Institute for Medical Research (US)
ORCID: Tracey, Kevin J.
Venue: Annual Review of Immunology
Publisher: Annual Reviews
Published: 2011-04-23
Volume: 29
Issue: 1
Pages: 139-162
ISSN: 0732-0582 (ISSN-L)
1545-3278
DOI: 10.1146/annurev-immunol-030409-101323
PMC: PMC4536551
OpenAlex: W2114445825
Cited by: 1,437
References: 148
Citations by year: 2026: 76 · 2025: 70 · 2024: 74 · 2023: 69 · 2022: 100 · 2021: 126 · 2020: 94 · 2019: 95 · 2018: 105 · 2017: 89 · 2016: 106 · 2015: 100 · 2014: 131 · 2013: 94 · 2012: 76
FWCI: 12.78
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Annual Review of Immunology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of General Medical Sciences (R01GM062508)
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 › Inflammasome and immune disorders
Keywords: HMGB1, sterile inflammation, infection, innate immunity, TLR4, HMGB1 release, HMGB1 signaling, cytokine production, tissue damage, ischemia, cell damage
MeSH terms: Animals, Humans, Immunity, Innate, Infections, Inflammation, Drug Delivery Systems, HMGB1 Protein, Toll-Like Receptor 4

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HMGB1 Is a Therapeutic Target for Sterile Inflammation and Infection

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