| First Author | Evavold CL | Year | 2018 |
| Journal | Immunity | Volume | 48 |
| Issue | 1 | Pages | 35-44.e6 |
| PubMed ID | 29195811 | Mgi Jnum | J:259899 |
| Mgi Id | MGI:6141670 | Doi | 10.1016/j.immuni.2017.11.013 |
| Citation | Evavold CL, et al. (2018) The Pore-Forming Protein Gasdermin D Regulates Interleukin-1 Secretion from Living Macrophages. Immunity 48(1):35-44.e6 |
| abstractText | The interleukin-1 (IL-1) family cytokines are cytosolic proteins that exhibit inflammatory activity upon release into the extracellular space. These factors are released following various cell death processes, with pyroptosis being a common mechanism. Recently, it was recognized that phagocytes can achieve a state of hyperactivation, which is defined by their ability to secrete IL-1 while retaining viability, yet it is unclear how IL-1 can be secreted from living cells. Herein, we report that the pyroptosis regulator gasdermin D (GSDMD) was necessary for IL-1beta secretion from living macrophages that have been exposed to inflammasome activators, such as bacteria and their products or host-derived oxidized lipids. Cell- and liposome-based assays demonstrated that GSDMD pores were required for IL-1beta transport across an intact lipid bilayer. These findings identify a non-pyroptotic function for GSDMD, and raise the possibility that GSDMD pores represent conduits for the secretion of cytosolic cytokines under conditions of cell hyperactivation. |
