Inflammatory caspases and their substrates

Inflammasomes are protein complexes comprised of a sensor, an adaptor, and a pro-caspase, activation of which leads to the cleavage and activation of Gasdermin D and the inflammatory cytokine IL-1β, resulting in the inflammatory form of cell death known as pyroptosis. Inflammasomes have been linked to a multitude of different conditions, including cancers and inflammatory diseases such as sepsis. Inflammasomes are divided into two categories, the canonical inflammasome that is activated through the detection of various detrimental stimuli, and the non-canonical inflammasome which is activated by LPS from Gram-negative bacteria. The aim of this project was to study the canonical and non-canonical inflammasomes in more detail though the use of various inhibitors, and then to identify novel inflammatory caspase substrates and study their role within the body. Through the use of proteomic analysis, several potential novel inflammatory caspase substrates were identified. After further analysis, IL-F3 was highlighted as a target for further study and validated in epithelial cell lines. This work provides the foundations for further study into the role of inflammatory caspases in the activation of this RNA-binding protein.