Inside, outside, upside down: damage-associated molecular-pattern molecules (DAMPs) and redox
Abstract
Immune responses are initiated and perpetuated by molecules derived from microorganisms pathogen-associated molecular-pattern molecules or from the damage or death of host cells [damage-associated molecular-pattern (DAMP) molecules]. Many DAMPs are nuclear or cytosolic proteins with defined intracellular function that, when released outside the cell following tissue injury, move from a reducing to an oxidizing milieu resulting in their functional denaturation. Here, we discuss the consequences of DAMP oxidation on the outcome of acute inflammation. We also suggest that, outside the cell, DAMPs might adopt novel conformations or alter the redox of the extracellular environment to more closely mimic the internal one, thereby avoiding oxidation-mediated inactivation and promoting pathology. We propose that chronic inflammation associated with autoimmunity, chronic viral infection and cancer is probably mediated by persistent release and function of DAMPs, promoting and promoted by a disordered redox environment.
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HMGB1 biological activities can switch from pro-inflammatory to anti-inflammatory depending on variables including oxidation state.
“That said, it should be noted that biological activities of HMGB1 may flip from pro-inflammatory to anti-inflammatory depending on multiple variables including its oxidation state [917–923].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [922]
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- Authors
- Rubartelli, A., & Lotze, M. T.
- Affiliations
- UPMC Hillman Cancer Center (US)
- Corresponding author
- Rubartelli, Anna
- Venue
- Trends in Immunology
- Publisher
- Elsevier BV
- Published
- 2007-10
- Volume
- 28
- Issue
- 10
- Pages
- 429-436
- ISSN
- 1471-4906 (ISSN-L)
- OpenAlex
- W2104414795
- Cited by
- 614
- References
- 67
- Citations by year
- 2026: 8 · 2025: 18 · 2024: 26 · 2023: 25 · 2022: 28 · 2021: 32 · 2020: 35 · 2019: 38 · 2018: 33 · 2017: 43 · 2016: 19 · 2015: 54 · 2014: 42 · 2013: 50 · 2012: 39
- FWCI
- 2.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pennsylvania Department of Health
- National Cancer Institute (P01CA101944)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Keywords
- damage-associated molecular patterns, redox conditions, acute inflammation, chronic inflammation, autoimmunity, chronic viral infection, cancer, protein denaturation, tissue damage, innate immunity
- MeSH terms
- Humans, Immunity, Innate, Inflammation, Neoplasms, Oxidation-Reduction, Proteins, Cytokines, Inflammation Mediators
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