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HMGB1-TLR4 signaling mediates liver I/R injury. HMGB1 is an early mediator of injury and inflammation in liver I/R, and TLR4 is the major receptor that is involved in the process by which the JNK MAPK/NF-κB pathway is activated. The release of HMGB1 in liver I/R requires TLR4 but not CD14. Different strategies of HMGB1-TLR4 pathway inhibition as indicated have been shown to reduce liver I/R injury.
