Abstract
A single cut to pyroptosis.
Highlights
Pyroptosis is a form of inflammatory cell death mediated by inflammatory caspases
The genetic screening results were confirmed through several experiments in mouse and human cells, showing that gasdermin D (GSDMD) is an essential molecule for noncanonical inflammasome-mediated pyroptosis
Kayagaki et al demonstrate that LPS-induced lethality is dramatically reduced in both Gsdmd-/- and Casp11-/- mice, which is critical in vivo data supporting that GSDMD is a key substrate of caspase-11 in pyroptosis
Summary
Pyroptosis is a form of inflammatory cell death mediated by inflammatory caspases. Two independent studies have recently demonstrated that inflammatory caspases cleave gasdermin D and the resulting N-terminal fragment of this protein mediates pyroptosis. In the canonical inflammasome (a multi-protein complex) pathway, caspase-1 is activated by inflammasome formation upon proinflammatory stimuli, such as microbial infection, and processes proinflammatory cytokines such as IL-1β and IL-18, triggering pyroptosis [1]. In contrast to the canonical inflammasome pathway, direct binding of caspase-11 to cytoplasmic lipopolysaccharide (LPS), a strong innate immune system stimulator, leads to noncanonical inflammasome activation to induce pyroptosis [2, 3].
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