Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 68, Issue 1, Pages 151-158Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-010-0450-3
Keywords
Inflammation; Toll-like receptors; Inflammasome; HIF-1; IL-1 beta; Caspase 1
Categories
Funding
- Royal Society [RG080474]
- Medway School of Pharmacy, University of Kent
Ask authors/readers for more resources
Inflammatory reactions to ssRNA viruses are induced by the endosomal Toll-like receptors (TLRs) 7 and 8. TLR7/8-mediated inflammatory reaction results in activation of the Nalp3 inflammasome via an unknown mechanism. Here we report for the first time that TLR7/8 mediate activation of xanthine oxidase (XOD) in an HIF-1 alpha-dependent manner. XOD produces uric acid and reactive oxygen species, which could activate Nalp3 and therefore induce activation of caspase 1, known to convert inactive pro-IL-1 beta into active IL-1 beta. Specific inhibition of the XOD activity attenuates TLR7/8-mediated activation of caspase 1 and IL-1 beta release. These results were obtained using human THP-1 myeloid macrophages. The findings were verified by conducting in vivo experiments on mice.
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