High-mobility group box 1 (HMGB1) protein: friend and foe.
HMGB1 was originally identified as a DNA-binding protein that functions as a structural co-factor critical for proper transcriptional regulation in somatic cells. Recent studies indicate that HMGB1 can be "passively released" into the extracellular milieu by necrotic and damaged somatic cells. Extracellular HMGB1 represents an optimal "necrotic marker" selected by the innate immune system to recognize tissue damage and initiate reparative responses. HMGB1 in the extracellular milieu promotes maturation of myeloid and plasmacytoid dendritic cells, and induces myocardial regeneration after infarction. However, extracellular HMGB1 also acts as a potent pro-inflammatory cytokine that contributes to the pathogenesis of diverse inflammatory and infectious disorders. A growing number of studies indicate that HMGB1 is a successful therapeutic target in experimental models of ischemia/reperfusion, acute respiratory distress syndrome, rheumatoid arthritis, sepsis, and cancer. From a clinical perspective, HMGB1 represents a current challenge that can be exploited orchestrate reparative responses while preventing its pathological potential. This article focus on the immuno-regulatory role of HMGB1 and its contribution to infectious and inflammatory disorders.
Ulloa
Luis
L
Center of Immunology and Inflammation, North Shore University Hospital, 350 Community Drive, Manhasset, NY 11030, USA. Contact@LuisUlloa.com
Messmer
Davorka
D
D000276:Adjuvants, Immunologic; D000818:Animals; D015551:Autoimmunity; D002467:Cell Nucleus / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000378:metabolism; D024243:HMGB1 Protein / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D007113:Immunity, Innate; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology*; D018836:Inflammation Mediators; D009336:Necrosis; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D018805:Sepsis / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D015398:Signal Transduction
D000276:Adjuvants, Immunologic; D016207:Cytokines; D024243:HMGB1 Protein; D018836:Inflammation Mediators; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic