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

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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; Lopez-Castejon, Gloria; Brough, David.

In: Journal of Biological Chemistry, Vol. 294, No. 21, 24.05.2019, p. 8325-8335.

Research output: Contribution to journalArticle

Harvard

Tapia, VS, Daniels, MJD, Palazón-Riquelme, P, Dewhurst, M, Luheshi, NM, Rivers-Auty, J, Green, J, Redondo-Castro, E, Kaldis, P, Lopez-Castejon, G & Brough, D 2019, 'The three cytokines IL-1β, IL-18, and IL-1α share related but distinct secretory routes', Journal of Biological Chemistry, vol. 294, no. 21, pp. 8325-8335. https://doi.org/10.1074/jbc.RA119.008009

APA

Tapia, V. S., Daniels, M. J. D., Palazón-Riquelme, P., Dewhurst, M., Luheshi, N. M., Rivers-Auty, J., Green, J., Redondo-Castro, E., Kaldis, P., Lopez-Castejon, G., & Brough, D. (2019). The three cytokines IL-1β, IL-18, and IL-1α share related but distinct secretory routes. Journal of Biological Chemistry, 294(21), 8325-8335. https://doi.org/10.1074/jbc.RA119.008009

CBE

Tapia VS, Daniels MJD, Palazón-Riquelme P, Dewhurst M, Luheshi NM, Rivers-Auty J, Green J, Redondo-Castro E, Kaldis P, Lopez-Castejon G, Brough D. 2019. The three cytokines IL-1β, IL-18, and IL-1α share related but distinct secretory routes. Journal of Biological Chemistry. 294(21):8325-8335. https://doi.org/10.1074/jbc.RA119.008009

MLA

Vancouver

Tapia VS, Daniels MJD, Palazón-Riquelme P, Dewhurst M, Luheshi NM, Rivers-Auty J et al. The three cytokines IL-1β, IL-18, and IL-1α share related but distinct secretory routes. Journal of Biological Chemistry. 2019 May 24;294(21):8325-8335. https://doi.org/10.1074/jbc.RA119.008009

Author

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 ; Lopez-Castejon, Gloria ; Brough, David. / The three cytokines IL-1β, IL-18, and IL-1α share related but distinct secretory routes. In: Journal of Biological Chemistry. 2019 ; Vol. 294, No. 21. pp. 8325-8335.

RIS

TY - JOUR

T1 - The three cytokines IL-1β, IL-18, and IL-1α share related but distinct secretory routes

AU - Tapia, Victor S

AU - Daniels, Michael J D

AU - Palazón-Riquelme, Pablo

AU - Dewhurst, Matthew

AU - Luheshi, Nadia M

AU - Rivers-Auty, Jack

AU - Green, Jack

AU - Redondo-Castro, Elena

AU - Kaldis, Philipp

AU - Lopez-Castejon, Gloria

AU - Brough, David

N1 - © 2019 Tapia et al.

PY - 2019/5/24

Y1 - 2019/5/24

N2 - 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.

AB - 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.

U2 - 10.1074/jbc.RA119.008009

DO - 10.1074/jbc.RA119.008009

M3 - Article

C2 - 30940725

VL - 294

SP - 8325

EP - 8335

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 1083-351X

IS - 21

ER -