Caspase-1 as a multifunctional inflammatory mediator: noncytokine maturation roles

Caspase-1 is an inflammatory caspase that is activated through formation of inflammasome complexes in response to both pathogen-derived and endogenous mediators. The most well-known function of active caspase-1 is to cleave the proforms of inflammatory cytokines IL-1 beta and -18 into their active forms in response to inflammatory stimuli in immune cells. However, recent evidence suggests that caspase-1 has multiple functions in addition to this cytokine maturation role and that it is at the center of many cell responses to stress and inflammation. The current review focuses on roles for caspase-1, and the closely related caspase-11, in inflammatory forms of cell death and protein cleavage and also in protein secretion. These alternative caspase-1 functions can influence inflammatory responses, not just in immune cells but in other cell types, such as epithelia, where inflammatory cytokine production may not be a primary cell function.