Generation of inducible immortalized bone marrow derived cell lines expressing mutant procaspase-1 C284A on a caspase-1 knock-out background

Introduction Caspase-1, belonging to the family of cystein proteases, is well-known for its involvement in IL-1b and IL-18 maturation. Although, caspase-1 is one of the best described caspase-family-members, open questions concerning autoinflammatory diseases, caused by procaspase-1 variants (e.g. ICE-Fever), remain. ICE-Fever patients suffer from chronic febrile episodes, although procaspase-1 variants show reduced enzymatic activity leading to limited IL-1b secretion. The paradox of reduced IL-1b secretion but increased inflammation led to the hypothesis, that CASP1-variants enhance alternative signaling pathways. However, the role of procaspase-1 variants and their interaction partners during IL-1b maturation or NFB activation is still poorly understood.