Figure 1.

HMGB1 is secreted actively (a) and passively (b) via different cascades. In active secretion, HMGB1 is acetylated or phosphorylated in the nucleus and then translocated into the cytoplasm, where it can then be secreted via lysosomes in hematopoietic cells or via not confirmed mechanisms in non-hematopoietic cells. In passive release, HMGB1 is released by dead cells confronting with tissue injury. Intracellular HMGB1 exists in the reduced form, while extracellular HMGB1 gradually transforms into fully reduced form. Thin black arrows indicate secretion or activation of the downstream targets.

DAMPs, damage-associated molecular patterns; HMGB, high mobility group box; IFNAR, interferon receptor; IFNβ, interferon β; IRFs, interferon regulatory factors; JAK, Janus kinase; PAMPS, pathogen-associated molecular patterns; PPRs, pattern recognition receptors.