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Caspase-1 (Interleukin-1 Converting Enzyme, ICE) is a proinflammatory enzyme mediating cleavage and secretion of the proinflammatory cytokines IL-1β and IL-18. Caspase-1 plays pivotal roles in the innate immune system and in inflammatory diseases like periodic fever syndromes, arthritis, or type-II-diabetes. In previous studies published by our group, genetic variants of procaspase-1 had been detected in patients suffering from autoinflammatory symptoms. Analyses of the procaspase-1 variants in HEK293T cells revealed reduced enzymatic activity of caspase-1 but enhanced ability to activate NF-κB signaling. The latter was mediated by enhanced CARD/CARD interactions of procaspase-1 with RIP2.

A transgenic in vitro cell model for the analysis of proinflammatory effects of naturally occurring genetic variants of caspase-1