title: Redox modulation of HMGB1-related signaling.
abstract: CONCLUSIONS
  In the cells' nuclei, high-mobility group box protein 1 (HMGB1) is a nonhistone chromatin-binding protein involved in the regulation of transcription. Extracellularly, HMGB1 acts as a danger molecule with properties of a proinflammatory cytokine. It can be actively secreted from myeloid cells or passively leak from any type of injured, necrotic cell. Increased serum levels of active HMGB1 are often found in pathogenic inflammatory conditions and correlate with worse prognoses in cancer, sepsis, and autoimmunity. By damaging cells, superoxide and peroxynitrite promote leakage of HMGB1.
  
  
  BACKGROUND
  The activity of HMGB1 strongly depends on its redox state: Inflammatory-active HMGB1 requires an intramolecular disulfide bond (Cys23 and Cys45) and a reduced Cys106. Oxidation of the latter blocks its stimulatory activity and promotes immune tolerance.
  
  
  RESULTS
  Reactive oxygen and nitrogen species create an oxidative environment and can be detoxified by superoxide dismutase (SOD), catalase, and peroxidases. Modifications of the oxidative environment influence HMGB1 activity.
  
  
  CONCLUSIONS
  In this review, we hypothesize that manipulations of an oxidative environment by SOD mimics or by hydrogen sulfide are prone to decrease tissue damage. Both the concomitant decreased HMGB1 release and its redox chemical modifications ameliorate inflammation and tissue damage.
authors: 1 Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich-Alexander-University of Erlangen-Nuremberg , Erlangen, Germany .
authors: Christina
authors: C
authors: Janko
authors: Milos
authors: M
authors: Filipović
authors: Luis E
authors: LE
authors: Munoz
authors: Christine
authors: C
authors: Schorn
authors: Georg
authors: G
authors: Schett
authors: Ivana
authors: I
authors: Ivanović-Burmazović
authors: Martin
authors: M
authors: Herrmann
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology; D010084:Oxidation-Reduction; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D016207:Cytokines; D024243:HMGB1 Protein
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