Investigating the role of inflammatory caspases in colorectal cancer

Abstract

Caspases are a group of proteolytic enzymes involved in the co-ordination of cellular processes, including cellular homeostasis, inflammation and apoptosis. The activation mechanisms and downstream signalling pathways mediated by inflammatory caspases are still being intensively researched. Inflammasome mediated activation of caspase-1 is responsible for the maturation and secretion of pro-inflammatory cytokines IL-1β and IL-18, and subsequent inflammatory response. Recently, non-canonical inflammasome activation (mediated by caspase-4 and -5 or their murine homolog, caspase-11) has been identified and shown to contribute to innate immune signalling in response to Gram-negative bacterial infection. Altered activity of caspases, particularly caspase-1, has been implicated in the development of intestinal diseases, such as inflammatory bowel disease (IBD) and colitis associated cancer (CAC). However, there is little known regarding the involvement of related inflammatory caspase members, murine caspase-11 and human caspases-4 and -5, during disease-associated intestinal inflammation