Targeting Inflammation Driven by HMGB1.
HMGB1
RAGE
TLR4
danger signal
drug target
inflammation
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2020
2020
Historique:
received:
14
01
2020
accepted:
02
03
2020
entrez:
9
4
2020
pubmed:
9
4
2020
medline:
30
3
2021
Statut:
epublish
Résumé
High mobility group box 1 (HMGB1) is a highly conserved, nuclear protein present in all cell types. It is a multi-facet protein exerting functions both inside and outside of cells. Extracellular HMGB1 has been extensively studied for its prototypical alarmin functions activating innate immunity, after being actively released from cells or passively released upon cell death. TLR4 and RAGE operate as the main HMGB1 receptors. Disulfide HMGB1 activates the TLR4 complex by binding to MD-2. The binding site is separate from that of LPS and it is now feasible to specifically interrupt HMGB1/TLR4 activation without compromising protective LPS/TLR4-dependent functions. Another important therapeutic strategy is established on the administration of HMGB1 antagonists precluding RAGE-mediated endocytosis of HMGB1 and HMGB1-bound molecules capable of activating intracellular cognate receptors. Here we summarize the role of HMGB1 in inflammation, with a focus on recent findings on its mission as a damage-associated molecular pattern molecule and as a therapeutic target in inflammatory diseases. Recently generated HMGB1-specific inhibitors for treatment of inflammatory conditions are discussed.
Identifiants
pubmed: 32265930
doi: 10.3389/fimmu.2020.00484
pmc: PMC7099994
doi:
Substances chimiques
Alarmins
0
Antigens, Neoplasm
0
HMGB1 Protein
0
Toll-Like Receptor 4
0
MOK protein, human
EC 2.7.11.22
Mitogen-Activated Protein Kinases
EC 2.7.11.24
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
484Subventions
Organisme : NCCIH NIH HHS
ID : R01 AT005076
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM063075
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM118182
Pays : United States
Informations de copyright
Copyright © 2020 Yang, Wang and Andersson.
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