Abstract
High mobility group box 1 (HMGB1) is a widely-expressed and highly-abundant protein that acts as an extracellular signal upon active secretion by immune cells or passive release by dead, dying, and injured cells. Both intracellular and extracellular HMGB1 play pivotal roles in regulation of the cellular response to stress. Targeting the translocation, release, and activity of HMGB1 can limit inflammation and reduce tissue damage during infection and sterile inflammation. Although the mechanisms contributing to HMGB1 biology are still under investigation, it appears that oxidative stress is a central regulator of HMGB1's translocation, release, and activity in inflammation and cell death (e.g., necrosis, apoptosis, autophagic cell death, pyroptosis, and NETosis). Thus, targeting HMGB1 with antioxidant compounds may be an attractive therapeutic strategy for inflammation-associated diseases such as sepsis, ischemia and reperfusion injury, arthritis, diabetes, and cancer.
Highlights
High mobility group box 1 (HMGB1), a widely-expressed and highly-abundant protein, plays multiple roles in physiological and pathological processes and is implicated in human health and diseases (Kang et al, 2014a), especially aging (Huang et al, 2014b) and inflammationassociated diseases (Andersson and Tracey, 2011; Harris et al, 2012)
HSP72, the main stress-induced Heat shock proteins (HSPs), inhibits oxidative stress-induced HMGB1 release by direct proteinto-protein interaction in macrophages (Tang et al, 2007a) (Figure 1A). These findings identify an essential role for HSP72 in blocking inflammation and preventing HMGB1 release in activated macrophages, it is not known whether an impaired heat shock response contributes to HMGB1 release in other cells
Since the discovery of HMGB1 in 1973 (Goodwin et al, 1973), the multi-faceted HMGB1 has recently been identified as an important mediator of infection and sterile inflammation, which has initiated a new field of translational medicine for targeting HMGB1 in disease (Kang et al, 2014a)
Summary
High mobility group box 1 (HMGB1), a widely-expressed and highly-abundant protein, plays multiple roles in physiological and pathological processes and is implicated in human health and diseases (Kang et al, 2014a), especially aging (Huang et al, 2014b) and inflammationassociated diseases (Andersson and Tracey, 2011; Harris et al, 2012). This review describes recent advances in our understanding of oxidative stress-mediated regulation of HMGB1 biology in inflammation and cell death (Green et al, 2009; Linkermann et al, 2014). Antioxidants such as quercetin (Tang et al, 2009), edaravone (Kato et al, 2009), epigallocatechin gallate (Li et al, 2007), and resveratrol (Xu et al, 2014b) significantly inhibit HMGB1 release in animal models of sepsis, suggesting that oxidative stress mediates HMGB1 secretion during infection.
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