Journal
SCIENTIFIC REPORTS
Volume 9, Issue -, Pages -Publisher
NATURE RESEARCH
DOI: 10.1038/s41598-019-53965-x
Keywords
-
Categories
Funding
- Teijin Pharma Limited
- FNS [310030_153010]
- Swiss National Science Foundation (SNF) [310030_153010] Funding Source: Swiss National Science Foundation (SNF)
Ask authors/readers for more resources
The nucleotide-binding oligomerization domain-like receptor family, pyrin domaincontaining 3 (NLRP3) inflammasome mediates caspase-1 activation and IL-1 beta processing and is implicated in autoinflammatory as well as other chronic inflammatory diseases. Recent studies have demonstrated that xanthine oxidoreductase (XOR) inhibition attenuated IL-1 beta secretion in activated macrophages, but the detailed mechanism of inhibition remains unclear. In this study, we report that febuxostat, an inhibitor of XOR, suppressed NLRP3 inflammasome-mediated IL-1 beta secretion and cell death by two mechanisms: in a mitochondrial ROS (mitoROS)-dependent and mitoROS-independent manner. MitoROS-independent effects of febuxostat were mediated by an increase of intracellular ATP and improved mitochondrial energetics via the activation of purine salvage pathway. Our findings suggest that cellular bioenergetics are important in regulating NLRP3 activation, and XOR inhibition may be clinically relevant in NLRP3-related inflammatory diseases.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available