Curcumin analogue AI-44 alleviates MSU-induced gouty arthritis in mice via inhibiting cathepsin B-mediated NLRP3 inflammasome activation.
Int Immunopharmacol
; 93: 107375, 2021 Apr.
Article
em En
| MEDLINE
| ID: mdl-33517224
ABSTRACT
NOD-like receptors (NLRs), as a part of intracellular pattern recognition receptors (PRR), are important regulators in innate immune system. The NLRP3 inflammasome which is a member of NLRs has been linked to several human inflammatory diseases. Gouty arthritis is triggered when the deposition of monosodium urate (MSU) crystals in joints induces acute inflammation characterized by the recruitment of macrophages and neutrophils. In this study, we explored the curcumin analogue AI-44 alleviated the gouty arthritis in mice via suppressing MSU engaging NLRP3 inflammasome activation. Furthermore, we demonstrated that AI-44 inhibited the interaction of cathepsin B and NLRP3 to prevent the activation of NLRP3 inflammasome. Moreover, we found AI-44 inhibited the enzyme activity of cathepsin B and bound to the key residue E122 in cytoplasm but not in lysosome. Collectively, these data suggest that AI-44 is a novel drug candidate for the treatment of gouty arthritis through targeting cathepsin B and inhibiting NLRP3 inflammasome activation.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Artrite Gotosa
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Curcumina
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Inflamassomos
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Proteína 3 que Contém Domínio de Pirina da Família NLR
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Int Immunopharmacol
Assunto da revista:
ALERGIA E IMUNOLOGIA
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FARMACOLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China