Caspases are a family of cysteine-aspartic acid proteases that cleave caspase proenzymes as well as other protein substrates. Caspases are well known for their role in apoptosis, but they also play a significant role in other cellular processes including inflammation (1). Apoptotic caspases include Caspases-3, -6, -7, -8, and -9. Meanwhile, human inflammatory caspases include Caspases-1, -4, -5, and -12. The role of Caspase-4 and -5 have been particularly difficult to study given that mice only express inflammatory Caspases-1,-11, and -12. Recent data suggests that human caspases-4 and -5 are orthologs of the murine Caspase-11 (1). Full length Caspase-4 is a 45 kDa protein while the cleaved isoform is only 36 kDa.
The inflammasome is an important protein complex involved in the innate immune response. An important role of the inflammasome is to promote cleavage and activation of IL-1β and IL-18 (2). Caspase-1 is one off the better characterized inflammatory caspases. It has been identified as part of the inflammasome and is responsible for cleaving proIL-1β and proIL-18. Caspase-4 was recently characterized for its role in activating the inflammasome. Sollberger et. al. suggests that Caspase-4 plays a role in activating Caspase-1 within the inflammasome (2). Further studies are needed to elucidate the exact mechanism by which Caspase-4 acts on Caspase-1, and whether these findings hold up in an in vivo model. Understanding the role of Caspase-4 in inflammation and immunity could potentially lead to novel treatments for autoimmune diseases.
Many groups are studying the role of Caspse-4 and inflammasome activation in a number of pathological conditions. Flood et. al. looked at levels of Caspase-4 expression in inflammatory bowel disease and colorectal cancer to determine its prognostic significance (3). Casson et. al. looked at Caspase-4 and its specific role in inflammasome activation during infection with gram negative bacteria (4). Meanwhile, there is much left to be understood about Caspase-4 and its role in both physiology and pathology.
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