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

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

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Abbreviations

AA:

Acute appendicitis

AGE:

Advanced glycation end products

AN:

Anorexia nervosa

ANCA:

Anti-neutrophil cytoplasmic antibodies

CSF:

Cerebrospinal fluid

CSS:

Churg–Strauss syndrome

CRP:

C-reactive protein

CD:

Crohn’s disease

DAMP:

Damage-associated molecular pattern

DCs:

Dendritic cells

HMGB1:

High-mobility group box 1

KD:

Kawasaki disease

JIA:

Juvenile idiopathic arthritis

IC:

Immune complexes

IBD:

Inflammatory bowel diseases

IFN:

Interferon

IL:

Interleukin

MPA:

Microscopic polyangiitis

MAPK:

Mitogen-activated protein kinases

NEC:

Necrotizing enterocolitis

NOD:

Nonobese diabetic

NF-κB:

Nuclear factor-kappa B

p-ANCAs:

Perinuclear anti-neutrophil cytoplasmic antibodies

RAGE:

Receptor for advanced glycation end products

RA:

Rheumatoid arthritis

SLE:

Systemic lupus erythematosus

TIM-3:

T cell immunoglobulin and mucin domain-3

TLR:

Toll-like receptor

TBI:

Traumatic brain injury

TGF:

Tumor growth factor

TNF:

Tumor necrosis factor

T1D:

Type 1 diabetes

UC:

Ulcerative colitis

WG:

Wegener granulomatosis

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Authors and Affiliations

  1. Department of Pediatric Sciences, University of Messina, 98100, Messina, Italy

    Valeria Chirico, Vincenzo Salpietro, Caterina Munafò, Maria Pia Calabrò, Teresa Arrigo & Carmelo Salpietro

  2. Department of Internal Medicine, University of Messina, Messina, Italy

    Antonio Lacquaniti & Michele Buemi

  3. Department of Internal Medicine, Mediterranean Institute for Transplantation and Advanced Specialized Therapies, ISMETT, Palermo, Italy

    Antonio Lacquaniti

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  1. Valeria Chirico
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  2. Antonio Lacquaniti
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  3. Vincenzo Salpietro
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  4. Caterina Munafò
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  5. Maria Pia Calabrò
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  6. Michele Buemi
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  7. Teresa Arrigo
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  8. Carmelo Salpietro
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Correspondence to Valeria Chirico.

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Communicated by David Nadal

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Chirico, V., Lacquaniti, A., Salpietro, V. et al. High-mobility group box 1 (HMGB1) in childhood: from bench to bedside. Eur J Pediatr 173, 1123–1136 (2014). https://doi.org/10.1007/s00431-014-2327-1

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  • DOI: https://doi.org/10.1007/s00431-014-2327-1

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