The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta.
摘要：
Generation of Interleukin (IL)-1β 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-1β processing is lost upon prior immunodepletion of Pycard. Moreover, expression of a dominant-negative form of Pycard in differentiated THP-1 cells blocks proIL-1β maturation and activation of inflammatory caspases induced by LPS in vivo. Thus, the inflammasome constitutes an important arm of the innate immunity.
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关键词：
Humans Cell-Free System Cell Line Hela Cells Inflammation Macromolecular Substances Adaptor Proteins, Signal Transducing Caspases Proteins Cytoskeletal Proteins
DOI：
10.1016/S1097-2765(02)00599-3
被引量：
年份：
2002
Elsevier
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Elsevier
Taylor & Francis
Ingenta
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