Hallmarks of NLRP3 inflammasome activation are observed in organotypic hippocampal slice culture.
Animals
Anti-Bacterial Agents
/ pharmacology
Caspase 1
/ metabolism
Cells, Cultured
Enzyme Activation
/ physiology
Hippocampus
/ metabolism
Interleukin-1beta
/ metabolism
Intracellular Signaling Peptides and Proteins
/ metabolism
Mice
Mice, Inbred C57BL
Microglia
/ metabolism
NLR Family, Pyrin Domain-Containing 3 Protein
/ metabolism
Nigericin
/ pharmacology
Organ Culture Techniques
Phosphate-Binding Proteins
/ metabolism
NLRP3
inflammasome
interleukin-1β
microglia
organotypic hippocampal slice culture
Journal
Immunology
ISSN: 1365-2567
Titre abrégé: Immunology
Pays: England
ID NLM: 0374672
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
20
03
2020
revised:
05
05
2020
accepted:
18
05
2020
pubmed:
24
5
2020
medline:
25
5
2021
entrez:
24
5
2020
Statut:
ppublish
Résumé
Microglial inflammation driven by the NACHT, LRR and PYD domain-containing protein 3 (NLRP3) inflammasome contributes to brain disease and is a therapeutic target. Most mechanistic studies on NLRP3 activation use two-dimensional pure microglial cell culture systems. Here we studied the activation of the NLRP3 inflammasome in organotypic hippocampal slices, which allowed us to investigate microglial NLRP3 activation in a three-dimensional, complex tissue architecture. Toll-like receptor 2 and 4 activation primed microglial inflammasome responses in hippocampal slices by increasing NLRP3 and interleukin-1β expression. Nigericin-induced NLRP3 inflammasome activation was dynamically visualized in microglia through ASC speck formation. Downstream caspase-1 activation, gasdermin D cleavage, pyroptotic cell death and interleukin-1β release were also detected, and these findings were consistent when using different NLRP3 stimuli such as ATP and imiquimod. NLRP3 inflammasome pathway inhibitors were effective in organotypic hippocampal slices. Hence, we have highlighted organotypic hippocampal slice culture as a valuable ex vivo tool to allow the future study of NLRP3 inflammasomes in a representative tissue section, aiding the discovery of further mechanistic insights and drug development.
Identifiants
pubmed: 32445196
doi: 10.1111/imm.13221
pmc: PMC7450173
doi:
Substances chimiques
Anti-Bacterial Agents
0
Gsdmd protein, mouse
0
IL1B protein, mouse
0
Interleukin-1beta
0
Intracellular Signaling Peptides and Proteins
0
NLR Family, Pyrin Domain-Containing 3 Protein
0
Nlrp3 protein, mouse
0
Phosphate-Binding Proteins
0
Caspase 1
EC 3.4.22.36
Nigericin
RRU6GY95IS
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
39-52Subventions
Organisme : Medical Research Council
ID : MR/T016515/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N003586/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N013751/1
Pays : United Kingdom
Informations de copyright
© 2020 The Authors. Immunology published by John Wiley & Sons Ltd.
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