Cutting Edge: High-Mobility Group Box 1 Preconditioning Protects against Liver Ischemia-Reperfusion Injury
Abstract
High mobility group box 1 (HMGB1) is a NF released extracellularly as a late mediator of lethality in sepsis and as an early mediator of inflammation following injury. Here we demonstrate that in contrast to the proinflammatory role of HMGB1, preconditioning with HMGB1 results in protection following hepatic ischemia/reperfusion (I/R). Pretreatment of mice with HMGB1 significantly decreased liver damage after I/R. The protection observed in mice pretreated with HMGB1 was associated with a higher expression of IL-1R-associated kinase-M, a negative regulator of TLR4 signaling, compared with controls. We thus explored the possibility that HMGB1 preconditioning was mediated through TLR4 activation. HMGB1 preconditioning failed to provide protection in TLR4 mutant (C3H/HeJ) mice, but successfully reduced damage in TLR4 wild-type (C3H/HeOuj) mice. Our studies demonstrate that in contrast to the role of HMGB1 as an early mediator of inflammation and organ damage in hepatic I/R, HMGB1 preconditioning can be protective.
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Reperfusion of ischemic tissues stimulates cytokine overproduction, including TNF, IL-1, and HMGB1, which contributes to the pathogenesis of resulting tissue damage.
“Reperfusion of ischemic tissues stimulates cytokine overproduction (e.g., TNF, IL-1, HMGB1), which contributes to the pathogenesis of resulting tissue damage (42)(43)(44).”
From Physiology and immunology of the cholinergic antiinflammatory pathway (2007) · cites this paper as [42]
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- Authors
- Izuishi, K., Tsung, A., Jeyabalan, G., Critchlow, N. D., Li, J., Tracey, K. J., Demarco, R. A., Lotze, M. T., Fink, M. P., Geller, D. A., & Billiar, T. R.
- Affiliations
- University of Pittsburgh (US)
- North Shore University Hospital (US)
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-06
- Volume
- 176
- Issue
- 12
- Pages
- 7154-7158
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2157119957
- Cited by
- 116
- References
- 28
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 4 · 2021: 2 · 2020: 4 · 2019: 2 · 2018: 5 · 2017: 5 · 2016: 6 · 2015: 6 · 2014: 8 · 2013: 6 · 2012: 5
- FWCI
- 7.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (P50 GM 53789, R01 GM52021, R01GM052021, R01GM037631, R01GM050441, R01 GM-37631, R01GM062508, P50GM053789, R01-GM-50441, R01-GM53789)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- HMGB1, preconditioning, hepatic ischemia-reperfusion injury, TLR4 signaling, liver injury, inflammation, sepsis, organ protection
- MeSH terms
- Amino Acid Sequence, Animals, HeLa Cells, Humans, Injections, Intravenous, Lipopolysaccharides, Liver, Male, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Mutant Strains, Molecular Sequence Data, Reperfusion Injury, Up-Regulation, Protein Serine-Threonine Kinases, Transplantation Conditioning, HMGB1 Protein, Intracellular Signaling Peptides and Proteins, Toll-Like Receptor 4, Mice, Interleukin-1 Receptor-Associated Kinases
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