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dc.contributor.authorYu, Shi
dc.contributor.authorGreen, Jack; orcid: 0000-0003-1108-3422
dc.contributor.authorWellens, Rose
dc.contributor.authorLopez‐Castejon, Gloria; orcid: 0000-0002-8585-3381
dc.contributor.authorBrough, David; orcid: 0000-0002-2250-2381; email: david.brough@manchester.ac.uk
dc.date.accessioned2021-05-20T16:39:06Z
dc.date.available2021-05-20T16:39:06Z
dc.date.issued2020-11-21
dc.date.submitted2020-03-02
dc.identifierhttps://chesterrep.openrepository.com/bitstream/handle/10034/624604/febs.15619.xml?sequence=2
dc.identifierhttps://chesterrep.openrepository.com/bitstream/handle/10034/624604/febs.15619.pdf?sequence=3
dc.identifier.citationThe FEBS Journal, volume 288, issue 10, page 3186-3196
dc.identifier.urihttp://hdl.handle.net/10034/624604
dc.descriptionFrom Wiley via Jisc Publications Router
dc.descriptionHistory: received 2020-03-02, rev-recd 2020-10-12, accepted 2020-11-02, pub-electronic 2020-11-21, pub-print 2021-05
dc.descriptionArticle version: VoR
dc.descriptionPublication status: Published
dc.descriptionFunder: Medical Research Council; Id: http://dx.doi.org/10.13039/501100000265; Grant(s): MR/N029992/1
dc.description.abstractThe release of interleukin (IL)‐1β from primary human monocytes in response to extracellular LPS occurs through the NACHT, LRR and PYD domains‐containing protein 3 (NLRP3) inflammasome. In primary monocytes, in response to LPS, NLRP3 inflammasome activation is characterized by an independence of K+ efflux and ASC speck formation and has been termed the ‘alternative’ pathway. Here, we report that pharmacological inhibition of V‐ATPase with bafilomycin A1 exacerbated LPS‐induced NLRP3 inflammasome activation in primary human monocytes. Inhibition of V‐ATPase in the presence of extracellular LPS led to NLRP3‐dependent, K+ efflux‐independent, ASC oligomerization and caspase‐1 activation. Although V‐ATPases are required for lysosomal acidification, we found that acidic lysosomal pH and protease activity were dispensable for this altered response, suggesting that V‐ATPase inhibition triggered alternative signalling events. Therefore, V‐ATPases may serve additional roles during NLRP3 inflammasome activation in primary human monocytes.
dc.languageen
dc.rightsLicence for VoR version of this article: http://creativecommons.org/licenses/by/4.0/
dc.sourceissn: 1742-464X
dc.sourceissn: 1742-4658
dc.subjectOriginal Article
dc.subjectOriginal Articles
dc.subjectalternative NLRP3 inflammasome
dc.subjectcaspase 1
dc.subjectcytokine
dc.subjectimmune cell
dc.subjectimmunology
dc.subjectinflammasome
dc.subjectinflammation
dc.subjectinterleukin 1
dc.subjectmonocyte
dc.subjectNLRP3
dc.titleBafilomycin A1 enhances NLRP3 inflammasome activation in human monocytes independent of lysosomal acidification
dc.typearticle
dc.date.updated2021-05-20T16:39:06Z
dc.date.accepted2020-11-02


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