title: High-mobility group box 1 (HMGB1) in childhood: from bench to bedside.
abstract: High-mobility group box protein 1 (HMGB1) is a nonhistone nuclear protein that has a dual function. Inside the cell, HMGB1 binds DNA, regulating transcription and determining chromosomal architecture. Outside the cell, HMGB1 activates the innate system and mediates a wide range of physiological and pathological responses. HMGB1 exerts these actions through differential engagement of multiple surface receptors, including Toll-like receptor (TLR)2, TLR4, and receptor for advanced glycation end products (RAGE). HMGB1 is implicated as a late mediator of sepsis and is also involved in inflammatory and autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. Interestingly, HMGB1 was associated with tumor progression, becoming a potential therapeutic target, due to its involvement in the resistance to chemotherapy. Its implication on the pathogenesis of systemic vasculitis and inflammatory bowel diseases has also been evaluated. Moreover, it regulates neuroinflammation after traumatic brain injuries or cerebral infectious diseases. The aim of this review is to analyze these different roles of HMGB1, both in physiological and pathological conditions, discussing clinical and scientific implications in the field of pediatrics.
  
  
  CONCLUSIONS
  HMGB1 plays a key role in several pediatric diseases, opening new scenarios for diagnostic biomarkers and therapeutic strategies development.
authors.affiliation: Department of Pediatric Sciences, University of Messina, 98100, Messina, Italy, valeriachirico@hotmail.it.
authors.forename: Valeria
authors.initials: V
authors.lastname: Chirico
authors.forename: Antonio
authors.initials: A
authors.lastname: Lacquaniti
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Salpietro
authors.forename: Caterina
authors.initials: C
authors.lastname: Munafò
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Calabrò
authors.forename: Michele
authors.initials: M
authors.lastname: Buemi
authors.forename: Teresa
authors.initials: T
authors.lastname: Arrigo
authors.forename: Carmelo
authors.initials: C
authors.lastname: Salpietro
mesh_terms: D001172:Arthritis, Rheumatoid / Q000378:metabolism; D001327:Autoimmune Diseases / Q000235:genetics / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D002648:Child; D018450:Disease Progression; D017127:Glycation End Products, Advanced / Q000378:metabolism; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism; D015398:Signal Transduction; D056647:Systemic Vasculitis / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D015415:Biomarkers; D017127:Glycation End Products, Advanced; D024243:HMGB1 Protein; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4