Glycyrrhizin attenuates caspase-11-dependent immune responses and coagulopathy by targeting high mobility group box 1.
Caspase-11
Non-canonical inflammasome
Pyroptosis
Sepsis
Journal
International immunopharmacology
ISSN: 1878-1705
Titre abrégé: Int Immunopharmacol
Pays: Netherlands
ID NLM: 100965259
Informations de publication
Date de publication:
Jun 2022
Jun 2022
Historique:
received:
22
12
2021
revised:
10
03
2022
accepted:
15
03
2022
pubmed:
28
3
2022
medline:
11
5
2022
entrez:
27
3
2022
Statut:
ppublish
Résumé
Caspase-11, a cytosolic endotoxin (lipopolysaccharide: LPS) receptor, mediates pyroptosis, coagulopathy and lethality in endoxemia and bacterial sepsis. The activation of caspase-11 requires high mobility group box 1 (HMGB1)-mediated translocation of LPS from the extracellular space to the cytosol. Here we show that HMGB1-dependent cytosolic delivery of LPS was blocked by glycyrrhizin, a medication to treat liver diseases. Glycyrrhizin competitively bound HMGB1 and thereby inhibiting the physical interaction between HMGB1 and LPS. Treatment of glycyrrhizin significantly attenuated caspase-11-dependent immune responses, coagulopathy, organ injury and lethality in endotoxemia and experimental sepsis. Together, our data suggest that pharmacological inhibition of the cytosolic delivery of LPS by glycyrrhizin might be a potential therapeutic strategy to treat sepsis, which is a leading cause of death in hospitals worldwide.
Identifiants
pubmed: 35339905
pii: S1567-5769(22)00197-7
doi: 10.1016/j.intimp.2022.108713
pii:
doi:
Substances chimiques
HMGB1 Protein
0
Lipopolysaccharides
0
Glycyrrhizic Acid
6FO62043WK
Caspases
EC 3.4.22.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
108713Informations de copyright
Copyright © 2022. Published by Elsevier B.V.