Rivers-Auty 2015 European_Journal_of_Immunology- Potassium Efflux Fires the Cannon.pdf (662.14 kB)
Download filePotassium efflux fires the canon: Potassium efflux as a common trigger for canonical and noncanonical NLRP3 pathways
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.
History
Publication title
European journal of immunologyVolume
45Issue
10Pagination
2758-2761ISSN
0014-2980Department/School
Tasmanian School of MedicinePublisher
Wiley-V C H Verlag GmbhPlace of publication
Po Box 10 11 61, Weinheim, Germany, D-69451Rights 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.Repository Status
- Open