Publications
Detailed Information
Auranofin prevents liver fibrosis by system Xc-mediated inhibition of NLRP3 inflammasome
Cited 18 time in
Web of Science
Cited 19 time in Scopus
- Authors
- Issue Date
- 2021-06
- Publisher
- Nature Publishing Group
- Citation
- Communications Biology, Vol.4 No.1, p. 824
- Abstract
- Using mouse models of liver fibrosis, Kim et al examined the mechanisms underlying the antifibrotic inhibition of the NLRP3 inflammasome by auranofin. They demonstrated that auranofin-induced inhibition of the NLRP3 inflammasome in bone marrow-derived macrophages and kupffer cells was mediated via inhibition of the cystine-glutamate antiporter, system Xc, which advances our understanding of the mechanism by which auranofin exerts its therapeutic effects. Demand for a cure of liver fibrosis is rising with its increasing morbidity and mortality. Therefore, it is an urgent issue to investigate its therapeutic candidates. Liver fibrosis progresses following 'multi-hit' processes involving hepatic stellate cells, macrophages, and hepatocytes. The NOD-like receptor protein 3 (NLRP3) inflammasome is emerging as a therapeutic target in liver fibrosis. Previous studies showed that the anti-rheumatic agent auranofin inhibits the NLRP3 inflammasome; thus, this study evaluates the antifibrotic effect of auranofin in vivo and explores the underlying molecular mechanism. The antifibrotic effect of auranofin is assessed in thioacetamide- and carbon tetrachloride-induced liver fibrosis models. Moreover, hepatic stellate cell (HSC), bone marrow-derived macrophage (BMDM), kupffer cell, and hepatocyte are used to examine the underlying mechanism of auranofin. Auranofin potently inhibits activation of the NLRP3 inflammasome in BMDM and kupffer cell. It also reduces the migration of HSC. The underlying molecular mechanism was inhibition of cystine-glutamate antiporter, system Xc. Auranofin inhibits system Xc activity and instantly induced oxidative burst, which mediated inhibition of the NLRP3 inflammasome in macrophages and HSCs. Therefore, to the best of our knowledge, we propose the use of auranofin as an anti-liver fibrotic agent.
- ISSN
- 2399-3642
- Files in This Item:
- There are no files associated with this item.
- Appears in Collections:
Item View & Download Count
Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.