The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta.

Details

Serval ID
serval:BIB_026D9182BA59
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta.
Journal
Molecular Cell
Author(s)
Martinon F., Burns K., Tschopp J.
ISSN
1097-2765 (Print)
ISSN-L
1097-2765
Publication state
Published
Issued date
2002
Volume
10
Number
2
Pages
417-426
Language
english
Abstract
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.
Keywords
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
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 15:19
Last modification date
20/08/2019 12:24
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