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The three cytokines IL-1β, IL-18, and IL-1α share related but distinct secretory routes

Tapia, Victor S ; Daniels, Michael J D ; Palazón-Riquelme, Pablo ; Dewhurst, Matthew ; Luheshi, Nadia M ; Rivers-Auty, Jack ; Green, Jack ; Redondo-Castro, Elena ; Kaldis, Philipp LU orcid and Lopez-Castejon, Gloria , et al. (2019) In Journal of Biological Chemistry 294(21). p.8325-8335
Abstract

Interleukin (IL)-1 family cytokines potently regulate inflammation, with the majority of the IL-1 family proteins being secreted from immune cells via unconventional pathways. In many cases, secretion of IL-1 cytokines appears to be closely coupled to cell death, yet the secretory mechanisms involved remain poorly understood. Here, we studied the secretion of the three best-characterized members of the IL-1 superfamily, IL-1α, IL-1β, and IL-18, in a range of conditions and cell types, including murine bone marrow-derived and peritoneal macrophages, human monocyte-derived macrophages, HeLa cells, and mouse embryonic fibroblasts. We discovered that IL-1β and IL-18 share a common secretory pathway that depends upon membrane permeability... (More)

Interleukin (IL)-1 family cytokines potently regulate inflammation, with the majority of the IL-1 family proteins being secreted from immune cells via unconventional pathways. In many cases, secretion of IL-1 cytokines appears to be closely coupled to cell death, yet the secretory mechanisms involved remain poorly understood. Here, we studied the secretion of the three best-characterized members of the IL-1 superfamily, IL-1α, IL-1β, and IL-18, in a range of conditions and cell types, including murine bone marrow-derived and peritoneal macrophages, human monocyte-derived macrophages, HeLa cells, and mouse embryonic fibroblasts. We discovered that IL-1β and IL-18 share a common secretory pathway that depends upon membrane permeability and can operate in the absence of complete cell lysis and cell death. We also found that the pathway regulating the trafficking of IL-1α is distinct from the pathway regulating IL-1β and IL-18. Although the release of IL-1α could also be dissociated from cell death, it was independent of the effects of the membrane-stabilizing agent punicalagin, which inhibited both IL-1β and IL-18 release. These results reveal that in addition to their role as danger signals released from dead cells, IL-1 family cytokines can be secreted in the absence of cell death. We propose that models used in the study of IL-1 release should be considered context-dependently.

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publishing date
type
Contribution to journal
publication status
published
in
Journal of Biological Chemistry
volume
294
issue
21
pages
8325 - 8335
publisher
American Society for Biochemistry and Molecular Biology
external identifiers
  • scopus:85066427369
  • pmid:30940725
ISSN
1083-351X
DOI
10.1074/jbc.RA119.008009
language
English
LU publication?
no
additional info
© 2019 Tapia et al.
id
1cd9d458-8bd8-4f2d-8d43-a9441bbaefc1
date added to LUP
2019-09-17 14:49:13
date last changed
2025-04-18 12:20:28
@article{1cd9d458-8bd8-4f2d-8d43-a9441bbaefc1,
  abstract     = {{<p>Interleukin (IL)-1 family cytokines potently regulate inflammation, with the majority of the IL-1 family proteins being secreted from immune cells via unconventional pathways. In many cases, secretion of IL-1 cytokines appears to be closely coupled to cell death, yet the secretory mechanisms involved remain poorly understood. Here, we studied the secretion of the three best-characterized members of the IL-1 superfamily, IL-1α, IL-1β, and IL-18, in a range of conditions and cell types, including murine bone marrow-derived and peritoneal macrophages, human monocyte-derived macrophages, HeLa cells, and mouse embryonic fibroblasts. We discovered that IL-1β and IL-18 share a common secretory pathway that depends upon membrane permeability and can operate in the absence of complete cell lysis and cell death. We also found that the pathway regulating the trafficking of IL-1α is distinct from the pathway regulating IL-1β and IL-18. Although the release of IL-1α could also be dissociated from cell death, it was independent of the effects of the membrane-stabilizing agent punicalagin, which inhibited both IL-1β and IL-18 release. These results reveal that in addition to their role as danger signals released from dead cells, IL-1 family cytokines can be secreted in the absence of cell death. We propose that models used in the study of IL-1 release should be considered context-dependently.</p>}},
  author       = {{Tapia, Victor S and Daniels, Michael J D and Palazón-Riquelme, Pablo and Dewhurst, Matthew and Luheshi, Nadia M and Rivers-Auty, Jack and Green, Jack and Redondo-Castro, Elena and Kaldis, Philipp and Lopez-Castejon, Gloria and Brough, David}},
  issn         = {{1083-351X}},
  language     = {{eng}},
  month        = {{05}},
  number       = {{21}},
  pages        = {{8325--8335}},
  publisher    = {{American Society for Biochemistry and Molecular Biology}},
  series       = {{Journal of Biological Chemistry}},
  title        = {{The three cytokines IL-1β, IL-18, and IL-1α share related but distinct secretory routes}},
  url          = {{http://dx.doi.org/10.1074/jbc.RA119.008009}},
  doi          = {{10.1074/jbc.RA119.008009}},
  volume       = {{294}},
  year         = {{2019}},
}