Intracellular Lipopolysaccharide Sensing as a Potential Therapeutic Target for Sepsis.
IL-1beta
LPS
caspases
outer membrane vesicles
pyroptosis
sepsis
Journal
Trends in pharmacological sciences
ISSN: 1873-3735
Titre abrégé: Trends Pharmacol Sci
Pays: England
ID NLM: 7906158
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
19
09
2018
revised:
20
12
2018
accepted:
07
01
2019
pubmed:
30
1
2019
medline:
7
3
2019
entrez:
30
1
2019
Statut:
ppublish
Résumé
Lipopolysaccharide (LPS) sensing in the cytosol by the noncanonical inflammasome leads to pyroptosis and NLRP3 inflammasome activation. This mechanism may be more critical for sepsis development than recognition of LPS by Toll-like receptor 4. LPS is directly binding to its intracellular receptor caspase-4/5/11, mediated by outer membrane vesicles and guanylate-binding proteins that deliver LPS to the cytosol and mediate access of caspases to LPS. Caspase-11-dependent cleavage of gasdermin D is discussed as a link between LPS-induced activation of caspases and pyroptosis or NLRP3 inflammasome activation. Finally, we highlight recently described inhibitors of cytosolic LPS-triggered noncanonical inflammasome activation that might be considered as potential drugs for the treatment of sepsis.
Identifiants
pubmed: 30691865
pii: S0165-6147(19)30001-X
doi: 10.1016/j.tips.2019.01.001
pii:
doi:
Substances chimiques
GSDMD protein, human
0
Inflammasomes
0
Intracellular Signaling Peptides and Proteins
0
Lipopolysaccharides
0
Neoplasm Proteins
0
Phosphate-Binding Proteins
0
Caspases
EC 3.4.22.-
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
187-197Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.