High-mobility group box 1 (HMGB1) in childhood: from bench to bedside.

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. Conclusion: HMGB1 plays a
key role in several pediatric diseases, opening new scenarios
for diagnostic biomarkers and therapeutic strategies
development.