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Updated: Jul 16, 2026
Bile Duct Ligation in Mice: Induction of Inflammatory Liver Injury and Fibrosis by Obstructive Cholestasis
Published on: February 10, 2015
NLRP3 inflammasome activation promotes liver inflammation and fibrosis in experimental biliary atresia
Junfeng Wang1, Min Du2, Lingdu Meng1
1Department 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.
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-1β 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.
