NLRP3 inflammasome activation promotes liver inflammation and fibrosis in experimental biliary atresia.
Dig Liver Dis
; 56(3): 458-467, 2024 Mar.
Article
em En
| MEDLINE
| ID: mdl-37635054
ABSTRACT
BACKGROUND:
Biliary atresia (BA) is characterized by a progressive fibroinflammatory cholangiopathy in early infants with unknown etiology. Although innate immune disorder is involved in its mechanism, role of NLRP3 inflammasome in BA remains largely undefined.AIM:
To explore the role of NLRP3 inflammasome in BA.METHODS:
The expressions of NLRP3 inflammasome-related genes were determined in BA patients. Role of NLRP3 inflammasome was evaluated using MCC950 in experimental BA. Furthermore, gadolinium chloride, a macrophage scavenger, was applied to validate the inflammasome's cellular localization. Finally, the effects of NLRP3 inflammasome activation on liver fibrosis were explored in vivo and vitro in experimental BA.RESULTS:
The components of NLRP3 inflammasome were up-regulated in BA patients. Inflammasome-related genes showed positively correlated with liver inflammation and fibrosis in BA patients. In experimental BA, inflammasome-related genes were up-regulated, and their expressions were inhibited by MCC950, which promoted mice growth, protected liver function, alleviated obstructive jaundice, inhibited liver inflammation, and reduced serum IL-1ß level. NLRP3 inflammasome was expressed in macrophages, and macrophage elimination exerted the same protective roles as MCC950 did in BA. Additionally, NLRP3 inflammasome activation promoted liver fibrosis in experimental BA.CONCLUSIONS:
NLRP3 inflammasome activation in macrophages promoted liver inflammation and fibrosis in experimental BA.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Atresia Biliar
/
Inflamassomos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Dig Liver Dis
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2024
Tipo de documento:
Article