Involvement of xanthine oxidase and hypoxia-inducible factor 1 in Toll-like receptor 7/8-mediated activation of caspase 1 and interleukin-1[beta]

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 oxidas...

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Bibliographic Details
Published in:Cellular and molecular life sciences : CMLS 2011-01, Vol.68 (1), p.151
Main Authors: Nicholas, Sally A, Bubnov, Vladimir V, Yasinska, Inna M, Sumbayev, Vadim V
Format: Article
Language:English
Subjects:
Biochemistry
Cellular biology
Hypoxia
Inflammatory diseases
Molecular biology
Viruses
Online Access:Get full text
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Summary: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. [PUBLICATION ABSTRACT]
ISSN:1420-682X
1420-9071
DOI:10.1007/s00018-010-0450-3