High-mobility Group Box 1 (HMGB1) in Childhood: from Bench to Bedside

Overview

Journal Eur J Pediatr

Specialty Pediatrics

Date 2014 May 10

PMID 24809802

Citations 9

Authors

Valeria Chirico

Antonio Lacquaniti

Vincenzo Salpietro

Caterina Munafo

Maria Pia Calabro

Michele Buemi

Teresa Arrigo

Carmelo Salpietro

Affiliations

Soon will be listed here.

Abstract

Unlabelled: 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.

Citing Articles

Advanced Biomarkers of Hepatotoxicity in Psychiatry: A Narrative Review and Recommendations for New Psychoactive Substances.

Golub A, Ordak M, Nasierowski T, Bujalska-Zadrozny M Int J Mol Sci. 2023; 24(11).

PMID: 37298365 PMC: 10253383. DOI: 10.3390/ijms24119413.

Free Light Chains, High Mobility Group Box 1, and Mortality in Hemodialysis Patients.

Lacquaniti A, Campo S, Falliti G, Caruso D, Gargano R, Giunta E J Clin Med. 2022; 11(23).

PMID: 36498479 PMC: 9739300. DOI: 10.3390/jcm11236904.

High-mobility group box chromosomal protein-1 deletion alleviates osteoporosis in OVX rat model via suppressing the osteoclastogenesis and inflammation.

Yu H, Zhou W, Zhong Z, Qiu R, Chen G, Zhang P J Orthop Surg Res. 2022; 17(1):232.

PMID: 35414033 PMC: 9004163. DOI: 10.1186/s13018-022-03110-8.

HMGB1: A pleiotropic activity.

Colavita L, Ciprandi G, Salpietro A, Cuppari C Pediatr Allergy Immunol. 2020; 31 Suppl 26:63-65.

PMID: 33236418 PMC: 7753284. DOI: 10.1111/pai.13358.

Novel therapeutic targets for allergic airway disease in children.

Giallongo A, Parisi G, Licari A, Pulvirenti G, Cuppari C, Salpietro C Drugs Context. 2019; 8:212590.

PMID: 31391855 PMC: 6668505. DOI: 10.7573/dic.212590.

References

Alleva L, Yang H, Tracey K, Clark I . High mobility group box 1 (HMGB1) protein: possible amplification signal in the pathogenesis of falciparum malaria. Trans R Soc Trop Med Hyg. 2005; 99(3):171-4. DOI: 10.1016/j.trstmh.2004.06.008. View

Nishitani C, Mitsuzawa H, Hyakushima N, Sano H, Matsushima N, Kuroki Y . The Toll-like receptor 4 region Glu24-Pro34 is critical for interaction with MD-2. Biochem Biophys Res Commun. 2005; 328(2):586-90. DOI: 10.1016/j.bbrc.2005.01.021. View

Tian J, Avalos A, Mao S, Chen B, Senthil K, Wu H . Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE. Nat Immunol. 2007; 8(5):487-96. DOI: 10.1038/ni1457. View

Sanders M, van Well G, Ouburg S, Morre S, Marceline van Furth A . Toll-like receptor 9 polymorphisms are associated with severity variables in a cohort of meningococcal meningitis survivors. BMC Infect Dis. 2012; 12:112. PMC: 3443431. DOI: 10.1186/1471-2334-12-112. View

Parkkinen J, Rauvala H . Interactions of plasminogen and tissue plasminogen activator (t-PA) with amphoterin. Enhancement of t-PA-catalyzed plasminogen activation by amphoterin. J Biol Chem. 1991; 266(25):16730-5. View

Kanakoudi-Tsakalidou F, Farmaki E, Tzimouli V, Taparkou A, Paterakis G, Trachana M . Simultaneous changes in serum HMGB1 and IFN-α levels and in LAIR-1 expression on plasmatoid dendritic cells of patients with juvenile SLE. New therapeutic options?. Lupus. 2014; 23(3):305-12. DOI: 10.1177/0961203313519157. View

Urbonaviciute V, Furnrohr B, Meister S, Munoz L, Heyder P, De Marchis F . Induction of inflammatory and immune responses by HMGB1-nucleosome complexes: implications for the pathogenesis of SLE. J Exp Med. 2008; 205(13):3007-18. PMC: 2605236. DOI: 10.1084/jem.20081165. View

Musumeci D, Roviello G, Montesarchio D . An overview on HMGB1 inhibitors as potential therapeutic agents in HMGB1-related pathologies. Pharmacol Ther. 2013; 141(3):347-57. DOI: 10.1016/j.pharmthera.2013.11.001. View

Koedel U . Toll-like receptors in bacterial meningitis. Curr Top Microbiol Immunol. 2009; 336:15-40. DOI: 10.1007/978-3-642-00549-7_2. View

10.

Agnello D, Wang H, Yang H, Tracey K, Ghezzi P . HMGB-1, a DNA-binding protein with cytokine activity, induces brain TNF and IL-6 production, and mediates anorexia and taste aversion. Cytokine. 2002; 18(4):231-6. DOI: 10.1006/cyto.2002.0890. View

11.

Devaraj S, Dasu M, Park S, Jialal I . Increased levels of ligands of Toll-like receptors 2 and 4 in type 1 diabetes. Diabetologia. 2009; 52(8):1665-8. PMC: 2709882. DOI: 10.1007/s00125-009-1394-8. View

12.

Wittemann B, Neuer G, Michels H, Truckenbrodt H, BAUTZ F . Autoantibodies to nonhistone chromosomal proteins HMG-1 and HMG-2 in sera of patients with juvenile rheumatoid arthritis. Arthritis Rheum. 1990; 33(9):1378-83. DOI: 10.1002/art.1780330910. View

13.

Messmer D, Yang H, Telusma G, Knoll F, Li J, Messmer B . High mobility group box protein 1: an endogenous signal for dendritic cell maturation and Th1 polarization. J Immunol. 2004; 173(1):307-13. DOI: 10.4049/jimmunol.173.1.307. View

14.

Buhimschi C, Baumbusch M, Dulay A, Oliver E, Lee S, Zhao G . Characterization of RAGE, HMGB1, and S100beta in inflammation-induced preterm birth and fetal tissue injury. Am J Pathol. 2009; 175(3):958-75. PMC: 2731116. DOI: 10.2353/ajpath.2009.090156. View

15.

Berger R, Bazaco M, Wagner A, Kochanek P, Fabio A . Trajectory analysis of serum biomarker concentrations facilitates outcome prediction after pediatric traumatic and hypoxemic brain injury. Dev Neurosci. 2010; 32(5-6):396-405. PMC: 3215242. DOI: 10.1159/000316803. View

16.

Junaid M, Kowal D, Barua M, Pullarkat P, Brooks S, Pullarkat R . Proteomic studies identified a single nucleotide polymorphism in glyoxalase I as autism susceptibility factor. Am J Med Genet A. 2004; 131(1):11-7. PMC: 1360505. DOI: 10.1002/ajmg.a.30349. View

17.

Bonthius D, Karacay B . Meningitis and encephalitis in children. An update. Neurol Clin. 2003; 20(4):1013-38, vi-vii. DOI: 10.1016/s0733-8619(02)00016-6. View

18.

Hoshina T, Kusuhara K, Ikeda K, Mizuno Y, Saito M, Hara T . High mobility group box 1 (HMGB1) and macrophage migration inhibitory factor (MIF) in Kawasaki disease. Scand J Rheumatol. 2008; 37(6):445-9. DOI: 10.1080/03009740802144143. View

19.

Kokkola R, Sundberg E, Ulfgren A, Palmblad K, Li J, Wang H . High mobility group box chromosomal protein 1: a novel proinflammatory mediator in synovitis. Arthritis Rheum. 2002; 46(10):2598-603. DOI: 10.1002/art.10540. View

20.

Jennette J, Falk R, Andrassy K, Bacon P, Churg J, Gross W . Nomenclature of systemic vasculitides. Proposal of an international consensus conference. Arthritis Rheum. 1994; 37(2):187-92. DOI: 10.1002/art.1780370206. View