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Background
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Chromogenic paranitroanilide substrate of caspase-1. Also cleaved by caspases-3, -4, and -7. Similar to amino acids 114-116 (VHD) of the IL-1B precursor, an endogenous substrate of caspase-1. Release of pNA is monitored at 405 nm (=9.160M -1 cm -1 ). Interleukin-1beta Converting Enzyme (ICE), now termed Caspase-1, is a cytoplasmic cysteine protease that cleaves inactive 31 kDa pro-IL-1beta to generate the active 17.5 kDa proinflammatory cytokine IL-1beta, the predominant form of IL-1 produced by human monocytes. This cytokine has been implicated in the pathogenesis of several diseases such as rheumatoid arthritis, inflammatory bowel disease, and septic shock. Caspase-1/ICE mRNA is found in a variety of cells such as peripheral blood monocytes, peripheral blood lymphocytes, peripheral blood neutrophils, and resting and activated peripheral blood T lymphocytes. The tissue distribution of Caspase-1/ICE suggests that the enzyme may have other substrates in addition to IL-1beta. Current hypotheses suggest that Caspase-1/ICE is able to cause apoptosis as well as activate inflammation in animal cells. Experiments have shown that Caspase-1/ICE has sequence homology with other mammalian apoptosis genes and that activation of Caspase-1/ICE or other ICE-related proteases (caspases)is required for anti-Fas mAb-induced apoptosis. The role of Caspase-4 in apoptosis is unclear but its substrate specificity is similar to that of Caspase-1/ICE.
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