NLRP3 Attenuates Intraocular Inflammation by Inhibiting AIM2-Mediated Pyroptosis Through the Phosphorylated Salt-Inducible Kinase 1/Sterol Regulatory Element Binding Transcription Factor 1 Pathway.
Journal
Arthritis & rheumatology (Hoboken, N.J.)
ISSN: 2326-5205
Titre abrégé: Arthritis Rheumatol
Pays: United States
ID NLM: 101623795
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
revised:
26
10
2022
received:
07
05
2022
accepted:
08
12
2022
medline:
17
5
2023
pubmed:
20
12
2022
entrez:
19
12
2022
Statut:
ppublish
Résumé
The NLRP3 inflammasome has been shown to be involved in the development of uveitis, but the exact mechanism remains elusive. This study was undertaken to explore the role of NLRP3 in the development of uveitis. First, Nlrp3-deficient mice were used to study the role of NLRP3 in experimental autoimmune diseases, such as experimental autoimmune uveitis (EAU) and experimental autoimmune encephalomyelitis (EAE). Next, the gathering of ASC, activation of caspase 1 and gasdermin D, and secretion of lactate dehydrogenase and interleukin-1β were detected to confirm macrophage pyroptosis and AIM2 activation in the Nlrp3 Surprisingly, our findings show that NLRP3 plays an antiinflammatory role in 2 models of EAU and EAE. Additionally, macrophages show an increased M1 activation and pyroptosis in Nlrp3 Our data demonstrate that NLRP3 inhibits AIM2 inflammasome-mediated EAU by regulating the p-SIK1/SREBF1 pathway, highlighting the therapeutic potential of targeting Nlrp3.
Substances chimiques
Inflammasomes
0
NLR Family, Pyrin Domain-Containing 3 Protein
0
DNA-Binding Proteins
0
Caspase 1
EC 3.4.22.36
Transcription Factors
0
Sterols
0
Interleukin-1beta
0
Nlrp3 protein, mouse
0
Aim2 protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
842-855Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2022 American College of Rheumatology.
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