| First Author | Muendlein HI | Year | 2020 |
| Journal | Science | Volume | 367 |
| Issue | 6484 | Pages | 1379-1384 |
| PubMed ID | 32193329 | Mgi Jnum | J:286605 |
| Mgi Id | MGI:6402875 | Doi | 10.1126/science.aay3878 |
| Citation | Muendlein HI, et al. (2020) cFLIPL protects macrophages from LPS-induced pyroptosis via inhibition of complex II formation. Science 367(6484):1379-1384 |
| abstractText | Cell death and inflammation are interdependent host responses to infection. During pyroptotic cell death, interleukin-1beta (IL-1beta) release occurs through caspase-1 and caspase-11-mediated gasdermin D pore formation. In vivo, responses to lipopolysaccharide (LPS) result in IL-1beta secretion. In vitro, however, murine macrophages require a second "danger signal" for the inflammasome-driven maturation of IL-1beta. Recent reports have shown caspase-8-mediated pyroptosis in LPS-activated macrophages but have provided conflicting evidence regarding the release of IL-1beta under these conditions. Here, to further characterize the mechanism of LPS-induced secretion in vitro, we reveal an important role for cellular FLICE-like inhibitory protein (cFLIP) in the regulation of the inflammatory response. Specifically, we show that deficiency of the long isoform cFLIPL promotes complex II formation, driving pyroptosis, and the secretion of IL-1beta in response to LPS alone. |
