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Development of a characterised tool kit for the interrogation of NLRP3 inflammasome-dependent responses

Redondo-Castro, Elena, Faust, Dorte, Fox, Simon, Baldwin, Alex G. ORCID:, Osborne, Simon, Haley, Michael J., Karran, Eric, Nuthall, Hugh, Atkinson, Peter J., Dawson, Lee A., Routledge, Carol, Allan, Stuart M., Freeman, Sally, Brownlees, Janet and Brough, David 2018. Development of a characterised tool kit for the interrogation of NLRP3 inflammasome-dependent responses. Scientific Reports 8 (1) , 5667. 10.1038/s41598-018-24029-3

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Inflammation is an established contributor to disease and the NLRP3 inflammasome is emerging as a potential therapeutic target. A number of small molecule inhibitors of the NLRP3 pathway have been described. Here we analysed the most promising of these inhibitor classes side by side to assess relative potency and selectivity for their respective putative targets. Assessed using ASC inflammasome-speck formation, and release of IL-1β, in both human monocyte/macrophage THP1 cells and in primary mouse microglia, we compared the relative potency and selectivity of P2X7 inhibitors, inflammasome inhibitors (diarylsulfonylurea vs. the NBC series), and caspase-1 inhibitors. In doing so we are now able to provide a well characterised small molecule tool kit for interrogating and validating inflammasome-dependent responses with a range of nanomolar potency inhibitors against established points in the inflammasome pathway.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Biosciences
Neuroscience and Mental Health Research Institute (NMHRI)
Publisher: Nature Publishing Group
ISSN: 2045-2322
Date of First Compliant Deposit: 9 April 2018
Date of Acceptance: 21 March 2018
Last Modified: 09 May 2023 03:21

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