| First Author | Heilig R | Year | 2018 |
| Journal | Eur J Immunol | Volume | 48 |
| Issue | 4 | Pages | 584-592 |
| PubMed ID | 29274245 | Mgi Jnum | J:261341 |
| Mgi Id | MGI:6151369 | Doi | 10.1002/eji.201747404 |
| Citation | Heilig R, et al. (2018) The Gasdermin-D pore acts as a conduit for IL-1beta secretion in mice. Eur J Immunol 48(4):584-592 |
| abstractText | The pro-inflammatory cytokine IL-1beta is well known for its role in host defense and the initiation of potent inflammatory responses. It is processed from its inactive pro-form by the inflammatory caspase-1 into its mature bioactive form, which is then released from the cell via an unconventional secretion mechanism. Recently, gasdermin-D has been identified as a new target of caspase-1. After proteolytical cleavage of gasdermin-D, the N-terminal fragment induces pyroptosis, a lytic cell death, by forming large permeability pores in the plasma membrane. Here we show using the murine system that gasdermin-D is required for IL-1beta secretion by macrophages, dendritic cells and partially in neutrophils, and that secretion is a cell-lysis-independent event. Liposome transport assays in vitro further demonstrate that gasdermin-D pores are large enough to allow the direct release of IL-1beta. Moreover, IL-18 and other small soluble cytosolic proteins can also be released in a lysis-independent but gasdermin-D-dependent mode, suggesting that the gasdermin-D pores allow passive the release of cytosolic proteins in a size-dependent manner. |
