Article: article from journal or magazin.
Caspase-11 activates a canonical NLRP3 inflammasome by promoting K(+) efflux.
European Journal of Immunology
Recognition of microbe-associated molecular patterns or endogenous danger signals by a subset of cytosolic PRRs results in the assembly of multiprotein signaling complexes, the so-called inflammasomes. Canonical inflammasomes are assembled by NOD-like receptor (NLR) or PYHIN family members and activate caspase-1, which promotes the induction of pyroptosis and the release of mature interleukin-1β/-18. Recently, a noncanonical inflammasome pathway was discovered that results in caspase-11 activation in response to bacterial lipopolysaccharide (LPS) in the cytosol. Interestingly, caspase-11 induces pyroptosis by itself, but requires NLRP3, the inflammasome adapter ASC, and caspase-1 to promote cytokine secretion. Here, we have studied the mechanism by which caspase-11 controls IL-1β secretion. Investigating NLRP3/ASC complex formation, we find that caspase-11 functions upstream of a canonical NLRP3 inflammasome. The activation of NLRP3 by caspase-11 during LPS transfection is a cell-intrinsic process and is independent of the release of danger signals. Furthermore, we show that active caspase-11 leads to a drop of intracellular potassium levels, which is necessary to activate NLRP3. Our study, therefore, sheds new light on the mechanism of noncanonical inflammasome signaling.
Animals, Apoptosis Regulatory Proteins/genetics, Apoptosis Regulatory Proteins/immunology, CARD Signaling Adaptor Proteins, Carrier Proteins/genetics, Carrier Proteins/immunology, Caspases/genetics, Caspases/immunology, Enzyme Activation/drug effects, Enzyme Activation/genetics, Enzyme Activation/immunology, Inflammasomes/genetics, Inflammasomes/immunology, Interleukin-1beta/genetics, Interleukin-1beta/immunology, Ion Transport/drug effects, Ion Transport/genetics, Ion Transport/immunology, Lipopolysaccharides/pharmacology, Mice, Mice, Knockout, NLR Family, Pyrin Domain-Containing 3 Protein, Potassium/immunology, Caspase-11, Inflammasome, Interleukin-1 beta (IL-1β), Lipopolysaccharide, NLRP3, Potassium efflux, Pyroptosis
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