cFLIP

Autor: Hayley I, Muendlein, David, Jetton, Wilson M, Connolly, Keith P, Eidell, Zoie, Magri, Irina, Smirnova, Alexander, Poltorak
Rok vydání: 2019
Předmět:
Zdroj: Science
ISSN: 1095-9203
Popis: Cell death and inflammation are interdependent host responses to infection. During pyroptotic cell death, interleukin-1β (IL-1β) release occurs through caspase-1 and caspase-11–mediated gasdermin D pore formation. In vivo, responses to lipopolysaccharide (LPS) result in IL-1β secretion. In vitro, however, murine macrophages require a second “danger signal” for the inflammasome-driven maturation of IL-1β. Recent reports have shown caspase-8–mediated pyroptosis in LPS-activated macrophages but have provided conflicting evidence regarding the release of IL-1β 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 cFLIP(L) promotes complex II formation, driving pyroptosis, and the secretion of IL-1β in response to LPS alone.
Databáze: OpenAIRE