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NLRP3 inflammasome activation promotes liver inflammation and fibrosis in experimental biliary atresia.
Wang, Junfeng; Du, Min; Meng, Lingdu; He, Shiwei; Zhu, Ye; Yang, Yifan; Ren, Xue; Huang, Yanlei; Sun, Song; Dong, Rui; Zheng, Shan; Chen, Gong.
Afiliação
  • Wang J; Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai 201102, PR China.
  • Du M; Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai 201102, PR China; Department of Pediatric Gastroenterology, Chengdu Women's and Children's Central Hospital, School
  • Meng L; Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai 201102, PR China.
  • He S; Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai 201102, PR China.
  • Zhu Y; Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai 201102, PR China.
  • Yang Y; Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai 201102, PR China.
  • Ren X; Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai 201102, PR China.
  • Huang Y; Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai 201102, PR China.
  • Sun S; Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai 201102, PR China.
  • Dong R; Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai 201102, PR China.
  • Zheng S; Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai 201102, PR China. Electronic address: szheng@shmu.edu.cn.
  • Chen G; Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai 201102, PR China. Electronic address: chengongzlp@fudan.edu.cn.
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.
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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
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

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