The HMGB1/RAGE axis triggers neutrophil-mediated injury amplification following necrosis

Toll-Like Receptor Signaling in Burn Wound Healing and Scarring

“…20 Furthermore, when HMGB1 was knocked out specifically in hepatic epithelial cells, there was a profound reduction of infiltrating neutrophils and inflammatory-gene expression, 21 suggesting that HMGB1 may be generally required for recruiting neutrophils to necrotic tissue where they may amplify tissue injury.…”

“…In addition, antibody to HMGB1 reduced hepatic I/R injury, and knocking out HMGB1 specifically in hepatic epithelial cells profoundly reduced numbers of infiltrating neutrophils and inflammatory gene expression. 21 Thus, blocking HMGB1 or its TLR4 receptor may benefit burn wound outcomes.…”

Hepatocyte-specific Hmgb1 Deletion

“…3 In contrast, hepatocyte-specific HMGB1 ablation leads to 100% survival following lethal acetaminophen intoxication due to prevention against necrosisinduced sterile inflammation, indicating an injury-promoting function of endogenous HMGB1 in the liver. 4 Dr. Natalia Nieto's lab: "Cell-and organ-specific Hmgb1 ablation was validated by IHC, which confirmed the absence of HMGB1 mostly in hepatocytes and not in other cells or organs such as the kidney." 5 Similarly, in the absence of any treatment, HMGB1-HC-KO mice show normal liver architecture.…”

Blue light reduces organ injury from ischemia and reperfusion

“…Damageassociated molecular patterns (DAMP), such as HMGB1, are released during I/R, and others and we have shown that HMGB1 is a key mediator of inflammation and cellular damage during liver I/R and ischemic AKI (23,41). Recently it has been shown that HMGB1 is released by necrotic cells and leads to neutrophil recruitment and injury amplification (24). We observed that blue light also reduced the systemic release of HMGB1.…”

“…Highmobility group box 1 (HMGB1), a nuclear DAMP, is a key mediator in the causal pathway of I/R-mediated neutrophil damage (23,24). We observed that during I/R, mice exposed to blue light exhibited reduced concentrations of serum HMGB1 (Fig.…”