The nuclear factor HMGB1 mediates hepatic injury after murine liver ischemia-reperfusion
By A. Tsung, Rohit Sahai, Hiroyuki Tanaka, A. Nakao, M. Fink, Michael Lotze, Huan Yang, Jianhua Li, Kevin J. Tracey, David A. Geller and 1 more. Journal of Experimental Medicine, 2005
1,173 citations recorded by the source corpus.
High-mobility group box 1 (HMGB1) is a nuclear factor that is released extracellularly as a late mediator of lethality in sepsis as well as after necrotic, but not apoptotic, death. Here we demonstrate that in contrast to the delayed role of HMGB1 in the systemic inflammation of sepsis, HMGB1 acts as an early mediator of inflammation and organ damage in hepatic ischemia reperfusion (I/R) injury. HMGB1 levels were increased during liver I/R as early as 1 h after reperfusion and then increased in a time-dependent manner up to 24 h. Inhibition of HMGB1 activity with neutralizing antibody significantly decreased liver damage after I/R, whereas administration of recombinant HMGB1 worsened I/R injury. Treatment with neutralizing antibody was associated with less phosphorylation of c-Jun NH2-terminal kinase and higher nuclear factor–κB DNA binding in the liver after I/R. Toll-like receptor 4 (TLR4)-defective (C3H/Hej) mice exhibited less damage in the hepatic I/R model than did wild-type (C3H/HeOuj) mice. Anti-HMGB1 antibody failed to provide protection in C3H/Hej mice, but successfully reduced damage in C3H/Ouj mice. Together, these results demonstrate that HMGB1 is an early mediator of injury and inflammation in liver I/R and implicates TLR4 as one of the receptors that is involved in the process.
Subfields: Clinical Biochemistry, Immunology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/3113cd2040245d1c241ec4de6c435edf8c08576c
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Citations in the corpus
- The inflammatory response to cell death. (2008, background): “Other studies showed that anti-HMGB1 antibodies could also reduce inflammation in livers that had sustained ischemia-reperfusion injury (32).”
- HMGB1: Endogenous Danger Signaling (2008, background): “In this model, tissue levels of HMGB1 are elevated as early as 1 h following reperfusion (118) and continue to increase for up to 24 h following the insult.”
- HMGB1 SIGNALS THROUGH TOLL-LIKE RECEPTOR (TLR) 4 AND TLR2 (2006, background): “suggested that even circulating HMGB1 requires intact TLR4 for effective signaling in vivo (17).”
- High mobility group box 1 protein interacts with multiple Toll-like receptors. (2006, result): “Although the participation of multiple receptors in HMGB1 signaling is somewhat surprising, similar results have been reported by other investigators, who also found that HMGB1 could activate cells through TLR-dependent and -independent pathways (43, 46).”
- The grateful dead: damage‐associated molecular pattern molecules and reduction/oxidation regulate immunity (2007, background): “CD14 shuttles LPS to MD2, in turn activating TLR4.”
- High‐mobility group box 1 (HMGB1) protein at the crossroads between innate and adaptive immunity (2007, background): “Acute liver injury, such as following ischemia and reperfusion of the organ, causes the rapid release of HMGB1, which triggers inflammation (37, 38).”
- Ischemia/Reperfusion (2016, positive): “Kupffer cells establishes a positive feedback for sustaining inflammatory responses after liver I/R that involves downstream expression of inflammatory cytokines occurring secondary to stimulation of NFκB-dependent transcription (71, 793, 794).”
- Cell Biology of Ischemia/Reperfusion Injury (2012, background): “This HMGB-1/TLR-4 positive feedback may play an important role in sustaining hepatic inflammation after I/R (Tsung et al., 2005a,b).”