Comment
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Interleukin-1? Converting Enzyme (!CE), also now known as Caspase-1, is a cytoplasmic cysteine protease that cleaves inactive 31 kDa pro-IL-1? to generate the active 17.5 kDa proinflammatory cytokine IL-1?, 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-1?. 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 caspase proteases is required for anti-Fas mAb-induced apoptosis. Ac-YVAD-CHO is a reversible inhibitor of caspase-1 and caspase-4 (Ki=200 pM for human recombinant caspase-1). It is more selective than Ac-VAD-CHO for caspase-1. Inhibition of caspases in cell extracts. Ac-YVADCHO inhibits anti-Fas induced apoptosis in L929-APO-1 cells. Generally, however, methylated peptide-FMK inhibitors (eg. Caspase-1/ICE Inhibitor 2, ABIN924918) are superior for use on live cells. It is recommended that stock solutions be prepared in high-purity DMSO (>99.9%), and then diluted into aqueous medium. Stock solutions should not be stored.
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