A rapid administration of GW4064 inhibits the NLRP3 inflammasome activation independent of farnesoid X receptor agonism.
FEBS Lett
; 591(18): 2836-2847, 2017 09.
Article
em En
| MEDLINE
| ID: mdl-28787755
ABSTRACT
GW4064 is a small molecule known to be an agonist of the nuclear farnesoid X receptor (FXR). We found that GW4064 inhibits the NLR family CARD domain containing 3 (NLRP3) inflammasome activation in an FXR-independent manner as evidenced by its similar inhibitory effect on NLRP3 inflammasome activation in FXR-deficient macrophages. Interestingly, GW4064 decreases the nigericin-induced oligomerization and ubiquitination of ASC which is critical for the NLRP3 inflammasome activation. In vivo results indicate that GW4064 could partially rescue the symptoms of NLRP3-dependent inflammatory disease models. These results not only necessitate cautious interpretation of the biological function of GW4064 as an FXR agonist, but also provide a potential therapeutic approach using GW4064 in the treatment of NLRP3-related diseases.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptores Citoplasmáticos e Nucleares
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Inflamassomos
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Proteína 3 que Contém Domínio de Pirina da Família NLR
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Isoxazóis
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article