Figure 2.

HMGB1 participates in inflammatory processes. HMGB1 exists in redox form after initially being passively released or actively secreted from cells. The redox form of HMGB1 can form a heterocomplex with CXCL12 and this complex binds to CXCR4, and macrophages are recruited after that. Macrophages secrete ROS and transform HMGB1 to disulfide form. The disulfide form of HMGB1 cannot interact with CXCL12 and CXCR. The disulfide HMGB1 binds to MD2-TLR4 complex and activates the NF-kB signaling pathway, proinflammatory cytokines are transcriptionally activated and secreted extracellularly subsequently. The disulfide HMGB1 is eventually oxidized to fully oxidized form and loses inflammation inducing capability. Black arrows indicate secretion or activation of the downstream targets, while blue arrows represent the alterations of the next inflammatory stage.

HMGB, high mobility group box; ROS, reactive oxygen species.