| First Author | Tapia VS | Year | 2019 |
| Journal | J Biol Chem | Volume | 294 |
| Issue | 21 | Pages | 8325-8335 |
| PubMed ID | 30940725 | Mgi Jnum | J:280521 |
| Mgi Id | MGI:6368451 | Doi | 10.1074/jbc.RA119.008009 |
| Citation | Tapia VS, et al. (2019) The three cytokines IL-1beta, IL-18, and IL-1alpha share related but distinct secretory routes. J Biol Chem 294(21):8325-8335 |
| abstractText | 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-1alpha, IL-1beta, 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-1beta 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-1alpha is distinct from the pathway regulating IL-1beta and IL-18. Although the release of IL-1alpha could also be dissociated from cell death, it was independent of the effects of the membrane-stabilizing agent punicalagin, which inhibited both IL-1beta 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. |
