Mice deficient in IL-1 beta-converting enzyme are defective in production of mature IL-1 beta and resistant to endotoxic shock.

Journal:

Cell 1995 Feb

Authors:

Li P, Allen H, Banerjee S, Franklin S, Herzog L, Johnston C, McDowell J, Paskind M, Rodman L, Salfeld J

Abstract

IL-1 beta-converting enzyme (ICE) cleaves pro-IL-1 beta to generate mature IL-1 beta. ICE is homologous to other proteins that have been implicated in apoptosis, including CED-3 and Nedd-2/lch-1. We generated ICE-deficient mice and observed that they are overtly normal but have a major defect in the production of mature IL-1 beta after stimulation with lipopolysaccharide. IL-1 alpha production is also impaired. ICE-deficient mice are resistant to endotoxic shock. Thymocytes and macrophages from
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the ICE-deficient animals undergo apoptosis normally. ICE therefore plays a dominant role in the generation of mature IL-1 beta, a previously unsuspected role in production of IL-1 alpha, but has no autonomous function in apoptosis.[less]

Mesh Headings:

Animals, Apoptosis, Base Sequence, Caspase 1, Chimera, Cysteine Endopeptidases, Cytokines, Female, Interleukin-1, Lipopolysaccharides, Macrophage Activation, Macrophages, Peritoneal, Male, Mice, Mice, Inbred C57BL, Molecular Sequence Data, RNA, Messenger, Sequence Deletion, Shock, Septic, Thymus Gland