HMGB1的不同氧化还原形式及其临床意义

High mobility group box 1 (HMGB1) is a member of HMG family, as well as a nuclear protein with extracellular inflammatory cytokine activity. It is released passively during cell injury and necrosis, and secreted actively by immune cells. The recruitment of inflammatory cells to damaged tissues and the induction of cytokines by different forms of HMGB1 involve different receptors. Disulfide HMGB1 promotes cytokine release via its interaction with the TLR4, whereas thiol HMGB1 forms a heterocomplex with the chemokine CXCL12 that acts exclusively via CXCR4. Reduced HMGB1 binds to RAGE, thus promoting Beclin1-dependent autophagy. Oxidized HMGB1 induces apoptosis via a Caspase-9/3 intrinsic pathway. Therefore, HMGB1 may be qualified as a target for therapeutic interventions. Understanding the effects of HMGB1 and its complex in the setting of oxidative stress may lead to the development of novel strategies to attenuate oxidative injury in various clinical situations, particularly those associated with chronic inflammation, including cancer.