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

Nicholas, Sally A. and Bubnov, Vladimir V. and Yasinska, Inna M. and Sumbayev, Vadim V. (2010) Involvement of xanthine oxidase and hypoxia-inducible factor 1 in Toll-like receptor 7/8-mediated activation of caspase 1 and interleukin-1? Cellular and Molecular Life Sciences, 68 (1). pp. 151-158. ISSN 1420-682X. E-ISSN 1420-9071. (doi:https://doi.org/10.1007/s00018-010-0450-3) (Access to this publication is currently restricted. You may be able to access a copy if URLs are provided)

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http://dx.doi.org/10.1007/s00018-010-0450-3

Abstract

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?-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? into active IL-1?. Specific inhibition of the XOD activity attenuates TLR7/8-mediated activation of caspase 1 and IL-1? release. These results were obtained using human THP-1 myeloid macrophages. The findings were verified by conducting in vivo experiments on mice.

Item Type: Article
Subjects: Q Science > QP Physiology (Living systems) > QP517 Biochemistry
Divisions: Faculties > Sciences > Medway School of Pharmacy
Depositing User: Vadim Sumbayev
Date Deposited: 08 Dec 2014 17:44 UTC
Last Modified: 08 May 2018 08:48 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/45799 (The current URI for this page, for reference purposes)
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