The Regulatory Role of High-Mobility Group Protein 1 in Sepsis-Related Immunity

Abstract

High-mobility group box 1 (HMGB1), a prototypical damage-associated molecular pattern (DAMP) molecule, participates in multiple processes of various inflammatory diseases through binding to its corresponding receptors. In the early phase, sepsis is mainly characterized as a multi-bacterial-induced complex, excessive inflammatory response accompanied by the release of pro-inflammatory mediators, which subsequently develops into immune paralysis. A growing number of in vivo and in vitro investigations reveal that HMGB1 plays a pivotal role in the processes of inflammatory response and immunosuppression of sepsis. Therefore, HMGB1 exerts an indispensable role in the immune disorder and life-threatening inflammatory syndrome of sepsis. HMGB1 mainly mediate the release of inflammatory factors via acting on immune cells, pyroptosis pathways and phosphorylating nuclear factor-κB. Moreover HMGB1 is also associated with the process of sepsis-related immunosuppression. Neutrophil dysfunction mediated by HMGB1 is also an aspect of the immunosuppressive mechanism of sepsis. Myeloid-derived suppressor cells (MDSCs), which are also one of the important cells that play an immunosuppressive effect in sepsis, may connect with HMGB1. Thence, further understanding of HMGB1-associated pathogenesis of sepsis may assist in development of promising treatment strategies. This review mainly discusses current perspectives on the roles of HMGB1 in sepsis-related inflammation and immunosuppressive process and its related internal regulatory mechanisms.