Interleukin-1β Maturation Triggers Its Relocation to the Plasma Membrane for Gasdermin-D-Dependent and -Independent Secretion
Summary: IL-1β requires processing by caspase-1 to generate the active, pro-inflammatory cytokine. Acute IL-1β secretion from inflammasome-activated macrophages requires caspase-1-dependent GSDMD cleavage, which also induces pyroptosis. Mechanisms of IL-1β secretion by pyroptotic and non-pyroptotic ...
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Format: | Article |
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Elsevier
2018-08-01
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Series: | Cell Reports |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718311173 |
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doaj-a43be258b327448fa6e72d48bc208d26 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mercedes Monteleone Amanda C. Stanley Kaiwen W. Chen Darren L. Brown Jelena S. Bezbradica Jessica B. von Pein Caroline L. Holley Dave Boucher Melanie R. Shakespear Ronan Kapetanovic Verena Rolfes Matthew J. Sweet Jennifer L. Stow Kate Schroder |
spellingShingle |
Mercedes Monteleone Amanda C. Stanley Kaiwen W. Chen Darren L. Brown Jelena S. Bezbradica Jessica B. von Pein Caroline L. Holley Dave Boucher Melanie R. Shakespear Ronan Kapetanovic Verena Rolfes Matthew J. Sweet Jennifer L. Stow Kate Schroder Interleukin-1β Maturation Triggers Its Relocation to the Plasma Membrane for Gasdermin-D-Dependent and -Independent Secretion Cell Reports |
author_facet |
Mercedes Monteleone Amanda C. Stanley Kaiwen W. Chen Darren L. Brown Jelena S. Bezbradica Jessica B. von Pein Caroline L. Holley Dave Boucher Melanie R. Shakespear Ronan Kapetanovic Verena Rolfes Matthew J. Sweet Jennifer L. Stow Kate Schroder |
author_sort |
Mercedes Monteleone |
title |
Interleukin-1β Maturation Triggers Its Relocation to the Plasma Membrane for Gasdermin-D-Dependent and -Independent Secretion |
title_short |
Interleukin-1β Maturation Triggers Its Relocation to the Plasma Membrane for Gasdermin-D-Dependent and -Independent Secretion |
title_full |
Interleukin-1β Maturation Triggers Its Relocation to the Plasma Membrane for Gasdermin-D-Dependent and -Independent Secretion |
title_fullStr |
Interleukin-1β Maturation Triggers Its Relocation to the Plasma Membrane for Gasdermin-D-Dependent and -Independent Secretion |
title_full_unstemmed |
Interleukin-1β Maturation Triggers Its Relocation to the Plasma Membrane for Gasdermin-D-Dependent and -Independent Secretion |
title_sort |
interleukin-1β maturation triggers its relocation to the plasma membrane for gasdermin-d-dependent and -independent secretion |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2018-08-01 |
description |
Summary: IL-1β requires processing by caspase-1 to generate the active, pro-inflammatory cytokine. Acute IL-1β secretion from inflammasome-activated macrophages requires caspase-1-dependent GSDMD cleavage, which also induces pyroptosis. Mechanisms of IL-1β secretion by pyroptotic and non-pyroptotic cells, and the precise functions of caspase-1 and GSDMD therein, are unresolved. Here, we show that, while efficient early secretion of endogenous IL-1β from primary non-pyroptotic myeloid cells in vitro requires GSDMD, later IL-1β release in vitro and in vivo proceeds independently of GSDMD. IL-1β maturation is sufficient for slow, caspase-1/GSDMD-independent secretion of ectopic IL-1β from resting, non-pyroptotic macrophages, but the speed of IL-1β release is boosted by inflammasome activation, via caspase-1 and GSDMD. IL-1β cleavage induces IL-1β enrichment at PIP2-enriched plasma membrane ruffles, and this is a prerequisite for IL-1β secretion and is mediated by a polybasic motif within the cytokine. We thus reveal a mechanism in which maturation-induced IL-1β trafficking facilitates its unconventional secretion. : Interleukin-1β is a potent pro-inflammatory cytokine whose dysregulated production drives a myriad of human diseases. Monteleone et al. uncover the trafficking mechanisms driving the unconventional secretion of mature interleukin-1β in non-pyroptotic and pyroptotic myeloid cells and reveal functions for caspase-1 and GSDMD therein. Keywords: interleukin-1, unconventional protein secretion, inflammasome, caspase-1, macrophage, neutrophil, gasdermin, pyroptosis, trafficking, phosphoinositides |
url |
http://www.sciencedirect.com/science/article/pii/S2211124718311173 |
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doaj-a43be258b327448fa6e72d48bc208d262020-11-25T01:15:01ZengElsevierCell Reports2211-12472018-08-0124614251433Interleukin-1β Maturation Triggers Its Relocation to the Plasma Membrane for Gasdermin-D-Dependent and -Independent SecretionMercedes Monteleone0Amanda C. Stanley1Kaiwen W. Chen2Darren L. Brown3Jelena S. Bezbradica4Jessica B. von Pein5Caroline L. Holley6Dave Boucher7Melanie R. Shakespear8Ronan Kapetanovic9Verena Rolfes10Matthew J. Sweet11Jennifer L. Stow12Kate Schroder13Institute for Molecular Bioscience (IMB), and IMB Centre for Inflammation and Disease Research, The University of Queensland, St. Lucia, Brisbane, QLD 4072, AustraliaInstitute for Molecular Bioscience (IMB), and IMB Centre for Inflammation and Disease Research, The University of Queensland, St. Lucia, Brisbane, QLD 4072, AustraliaInstitute for Molecular Bioscience (IMB), and IMB Centre for Inflammation and Disease Research, The University of Queensland, St. Lucia, Brisbane, QLD 4072, AustraliaInstitute for Molecular Bioscience (IMB), and IMB Centre for Inflammation and Disease Research, The University of Queensland, St. Lucia, Brisbane, QLD 4072, AustraliaInstitute for Molecular Bioscience (IMB), and IMB Centre for Inflammation and Disease Research, The University of Queensland, St. Lucia, Brisbane, QLD 4072, AustraliaInstitute for Molecular Bioscience (IMB), and IMB Centre for Inflammation and Disease Research, The University of Queensland, St. Lucia, Brisbane, QLD 4072, AustraliaInstitute for Molecular Bioscience (IMB), and IMB Centre for Inflammation and Disease Research, The University of Queensland, St. Lucia, Brisbane, QLD 4072, AustraliaInstitute for Molecular Bioscience (IMB), and IMB Centre for Inflammation and Disease Research, The University of Queensland, St. Lucia, Brisbane, QLD 4072, AustraliaInstitute for Molecular Bioscience (IMB), and IMB Centre for Inflammation and Disease Research, The University of Queensland, St. Lucia, Brisbane, QLD 4072, AustraliaInstitute for Molecular Bioscience (IMB), and IMB Centre for Inflammation and Disease Research, The University of Queensland, St. Lucia, Brisbane, QLD 4072, AustraliaInstitute for Molecular Bioscience (IMB), and IMB Centre for Inflammation and Disease Research, The University of Queensland, St. Lucia, Brisbane, QLD 4072, AustraliaInstitute for Molecular Bioscience (IMB), and IMB Centre for Inflammation and Disease Research, The University of Queensland, St. Lucia, Brisbane, QLD 4072, AustraliaInstitute for Molecular Bioscience (IMB), and IMB Centre for Inflammation and Disease Research, The University of Queensland, St. Lucia, Brisbane, QLD 4072, AustraliaInstitute for Molecular Bioscience (IMB), and IMB Centre for Inflammation and Disease Research, The University of Queensland, St. Lucia, Brisbane, QLD 4072, Australia; Corresponding authorSummary: IL-1β requires processing by caspase-1 to generate the active, pro-inflammatory cytokine. Acute IL-1β secretion from inflammasome-activated macrophages requires caspase-1-dependent GSDMD cleavage, which also induces pyroptosis. Mechanisms of IL-1β secretion by pyroptotic and non-pyroptotic cells, and the precise functions of caspase-1 and GSDMD therein, are unresolved. Here, we show that, while efficient early secretion of endogenous IL-1β from primary non-pyroptotic myeloid cells in vitro requires GSDMD, later IL-1β release in vitro and in vivo proceeds independently of GSDMD. IL-1β maturation is sufficient for slow, caspase-1/GSDMD-independent secretion of ectopic IL-1β from resting, non-pyroptotic macrophages, but the speed of IL-1β release is boosted by inflammasome activation, via caspase-1 and GSDMD. IL-1β cleavage induces IL-1β enrichment at PIP2-enriched plasma membrane ruffles, and this is a prerequisite for IL-1β secretion and is mediated by a polybasic motif within the cytokine. We thus reveal a mechanism in which maturation-induced IL-1β trafficking facilitates its unconventional secretion. : Interleukin-1β is a potent pro-inflammatory cytokine whose dysregulated production drives a myriad of human diseases. Monteleone et al. uncover the trafficking mechanisms driving the unconventional secretion of mature interleukin-1β in non-pyroptotic and pyroptotic myeloid cells and reveal functions for caspase-1 and GSDMD therein. Keywords: interleukin-1, unconventional protein secretion, inflammasome, caspase-1, macrophage, neutrophil, gasdermin, pyroptosis, trafficking, phosphoinositideshttp://www.sciencedirect.com/science/article/pii/S2211124718311173 |