Rivers-Auty 2015 European_Journal_of_Immunology- Potassium Efflux Fires the Cannon.pdf (662.14 kB)Download file
Potassium efflux fires the canon: Potassium efflux as a common trigger for canonical and noncanonical NLRP3 pathways
journal contributionposted on 2023-05-20, 08:29 authored by Jack AutyJack Auty, Brough, D
Murine caspase-11 and its human orthologues, caspase-4 and caspase-5, activate an inflammatory response following cytoplasmic recognition of cell wall constituents from Gram-negative bacteria, such as LPS. This inflammatory response involves pyroptotic cell death and the concomitant release of IL-1α, as well as the production of IL-1β and IL-18 through the noncanonical NLR family, pyrin domain containing 3 (NLRP3) pathway. This commentary discusses three papers in this issue of the European Journal of Immunology that advance our understanding of the roles of caspase-11, -4, and -5 in the noncanonical pathway. By utilizing the new gene editing technique, clustered regularly interspaced short palindromic repeats (CRISPR), as well as sensitive cell imaging techniques, these papers establish that cytoplasmic LPS-dependent IL-1β production requires the NLRP3 inflammasome and that its activation is dependent on K(+) efflux, whereas IL-1α release and pyroptotic cell death pathways are NLRP3-independent. These findings expand on previous research implicating K(+) efflux as the principal trigger for NLRP3 activation and suggest that canonical and noncanonical NLRP3 pathways are not as dissimilar as first thought.
Publication titleEuropean journal of immunology
Department/SchoolTasmanian School of Medicine
PublisherWiley-V C H Verlag Gmbh
Place of publicationPo Box 10 11 61, Weinheim, Germany, D-69451
Rights statement© 2015 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim. This is the pre-peer reviewed version which has been published in final form at the DOI below. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.