The role of HMGB1 in inflammatory skin diseases.

High-mobility group box 1 protein (HMGB1) is a highly abundant, non-histone nuclear protein that can serve as an alarmin to promote the pathogenesis of inflammatory diseases. In response to various stimuli, HMGB1 can translocate from the nucleus to the cytoplasm as well as the extracellular space through passive or active release, accompanied with different post-translational modifications. Depending on the redox state of three cysteine residues, HMGB1 determines its activity to induce cytokine production or tissue repair through binding with several different receptors. In addition, HMGB1 can form immunostimulatory complexes with cytokines and other endogenous/exogenous molecules and synergistically enhance their biological effect. Cell death is an important source of HMGB1 and major cell death forms such as apoptosis, necrosis and pyroptosis can modulate the redox state of HMGB1. In various human skin diseases as well as animal models, HMGB1 levels in cytoplasm, tissue and blood are increased and blockade of HMGB1 attenuates disease severity in animal models. These findings indicate that HMGB1 can serve as a unique biomarker as well as a target of new therapy in many inflammatory skin diseases.