Article: article from journal or magazin.
The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta.
Generation of Interleukin (IL)-1beta via cleavage of its proform requires the activity of caspase-1 (and caspase-11 in mice), but the mechanism involved in the activation of the proinflammatory caspases remains elusive. Here we report the identification of a caspase-activating complex that we call the inflammasome. The inflammasome comprises caspase-1, caspase-5, Pycard/Asc, and NALP1, a Pyrin domain-containing protein sharing structural homology with NODs. Using a cell-free system, we show that proinflammatory caspase activation and proIL-1beta processing is lost upon prior immunodepletion of Pycard. Moreover, expression of a dominant-negative form of Pycard in differentiated THP-1 cells blocks proIL-1beta maturation and activation of inflammatory caspases induced by LPS in vivo. Thus, the inflammasome constitutes an important arm of the innate immunity.
Adaptor Proteins, Signal Transducing, Apoptosis Regulatory Proteins, Blotting, Western, Caspase 1/metabolism, Caspases/metabolism, Cell Line, Cell-Free System, Cytoskeletal Proteins/genetics, Cytoskeletal Proteins/metabolism, Enzyme Activation, Hela Cells, Humans, Inflammation/enzymology, Inflammation/metabolism, Interleukin-1/metabolism, Lipopolysaccharides/pharmacology, Macromolecular Substances, Protein Precursors/metabolism, Protein Processing, Post-Translational/drug effects, Proteins/metabolism
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