Pathophysiological function of HMGB1 as a late-acting mediator of inflammation

High mobility group box chromosomal protein (HMGB1), an abundant eukaryotic nonhistone chromosomal protein, is previously known as a nuclear DNA-binding protein that stabilizes the structure and function of chromatin, regulates gene transcription. Recent studies identify that extracellular HMGB1 as a late mediator of endotoxemia and sepsis.HMGB1 is released by activated macrophages,induces the release of other proinflammatory mediators,and mediates lethality when overexpressed. It may also be a key signal for eliciting immune responses to cellular injury and death.Moreover,the late kinetics of HMGB1,in compared with other proinflammatory cytokines such as TNF and IL-1,suggest that targeting HMGB1 may provide a wide and clinically accessible therapeutic window.Three independent strategies to inhibit HMGB1 release and action are now available:anti-HMGB1 antibodies,A box,and ethyl pyruvate. This review covers the general features of HMGB1 and progress in research on its newly role as a cytokine participating in the development of sepsis.