Lycorine ameliorates bleomycin-induced pulmonary fibrosis via inhibiting NLRP3 inflammasome activation and pyroptosis.
Pharmacol Res
; 158: 104884, 2020 08.
Article
em En
| MEDLINE
| ID: mdl-32428667
ABSTRACT
Idiopathic pulmonary fibrosis (IPF) is a chronic and irreversible lung disease with limited therapeutic strategies. Lycorine (LYC), an alkaloid isolated from Amaryllidaceae family plants, exhibits effective anti-inflammatory, antiviral, and anti-tumor activities. In this study, we attempted to determine the effect of LYC on bleomycin (BLM)-induced IPF and NLRP3 inflammasome activation. Our results demonstrated that the LYC treatment ameliorated BLM-induced pulmonary fibrosis and inflammation in mice. LYC inhibited active Caspase-1 expression and lactate dehydrogenase (LDH) release during BLM-induced acute lung injury (ALI) in mice. Furthermore, our in vitro assay showed that LYC inhibited LPS/Nigericin- or LPS/ATP-induced NACHT, LRP and PYD domains-containing protein 3 (NLRP3) inflammasome activation, and pyroptosis in bone marrow-derived macrophages (BMDMs). Mechanically, LYC could disturb the interaction of NLRP3 with apoptosis-associated speck-like protein containing a CARD (ASC) by targeting the pyrin domain (PYD) on Leu9, Leu50, and Thr53. Our findings indicate that LYC ameliorated BLM-induced pulmonary fibrosis by inhibiting NLRP3 inflammasome activation and pyroptosis through targeting the PYD domain of ASC. Thus, LYC might be a potential therapeutic agent for pulmonary inflammation and fibrosis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fenantridinas
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Fibrose Pulmonar
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Bleomicina
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Alcaloides de Amaryllidaceae
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Piroptose
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Proteína 3 que Contém Domínio de Pirina da Família NLR
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Pharmacol Res
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China