Interleukin-1β maturation triggers its relocation to the plasma membrane for gasdermin-D-dependent and -independent secretion
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, an...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Elsevier
2018
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| _version_ | 1826257628783706112 |
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| author | Monteleone, M Stanley, AC Chen, KW Brown, DL Bezbradica, JS Von Pein, JB Holley, CL Boucher, D Shakespear, MR Kapetanovic, R Rolfes, V Sweet, MJ Stow, JL Schroder, K |
| author_facet | Monteleone, M Stanley, AC Chen, KW Brown, DL Bezbradica, JS Von Pein, JB Holley, CL Boucher, D Shakespear, MR Kapetanovic, R Rolfes, V Sweet, MJ Stow, JL Schroder, K |
| author_sort | Monteleone, M |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T18:21:11Z |
| format | Journal article |
| id | oxford-uuid:065a254d-dc37-4e9b-9f6a-10941f0bb209 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:21:11Z |
| publishDate | 2018 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:065a254d-dc37-4e9b-9f6a-10941f0bb2092022-03-26T09:02:04ZInterleukin-1β maturation triggers its relocation to the plasma membrane for gasdermin-D-dependent and -independent secretionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:065a254d-dc37-4e9b-9f6a-10941f0bb209EnglishSymplectic Elements at OxfordElsevier2018Monteleone, MStanley, ACChen, KWBrown, DLBezbradica, JSVon Pein, JBHolley, CLBoucher, DShakespear, MRKapetanovic, RRolfes, VSweet, MJStow, JLSchroder, KIL-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. |
| spellingShingle | Monteleone, M Stanley, AC Chen, KW Brown, DL Bezbradica, JS Von Pein, JB Holley, CL Boucher, D Shakespear, MR Kapetanovic, R Rolfes, V Sweet, MJ Stow, JL Schroder, K Interleukin-1β maturation triggers its relocation to the plasma membrane for gasdermin-D-dependent and -independent secretion |
| title | 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_short | 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 |
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