A Janus tale of two active high mobility group box 1 (HMGB1) redox states.
High mobility group box 1 (HMGB1), the prototypic damage-associated molecular pattern molecule, is released at sites of inflammation and/or tissue damage. There, it promotes cytokine production and chemokine production/cell migration. New work shows that the redox status of HMGB1 distinguishes its cytokine-inducing and chemokine activity. Reduced all-thiol-HMGB1 has sole chemokine activity, whereas disulfide-HMGB1 has only cytokine activity, and oxidized, denatured HMGB1 has neither. Autophagy (programmed cell survival) and apoptosis (programmed cell death) have been implicated in controlling both innate and adaptive immune functions. Reduced HMGB1 protein promotes autophagy, whereas oxidized HMGB1 promotes apoptosis. Thus, the differential activity of HMGB1 in immunity, inflammation and cell death depends on the cellular redox status within tissues.
Department of Surgery, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States of America. tangd2@upmc.edu
Daolin
D
Tang
Timothy R
TR
Billiar
Michael T
MT
Lotze
D000818:Animals; D004194:Disease; D024243:HMGB1 Protein / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism
D024243:HMGB1 Protein; D017382:Reactive Oxygen Species