[HTML][HTML] The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-β

F Martinon, K Burns, J Tschopp - Molecular cell, 2002 - cell.com
F Martinon, K Burns, J Tschopp
Molecular cell, 2002cell.com
Abstract 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 …
Abstract
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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