Is caspase-12 implicated in inflammation?
A hallmark in the functional analysis of a gene is the generation of knockout animals. Caspase-1- and -11-deficient mice were challenged with proinflammatory stimuli, such as lipopolysaccharide (LPS) and tumor necrosis factor (TNF).2,3 These and other experiments led to the conclusion that caspase-1 and -11 are essential for the maturation and release of the proinflammatory cytokines IL-1 and IL-18.2,3 Both pro-IL-1 and pro-IL-18 are produced as biologically inactive precursor cytokines of 31 kDa that require cleavage by caspase-1 before the 17 kDa mature form is released from the cytosol. Monocytes from caspase-1- and -11-deficient mice display lower levels of other cytokines such as IL-1, TNF-, IL-6 and IFN- in endotoxemia.2,3,4 Furthermore, both caspase-1 and -11 knockout mice are resistant to septic shock induced by the intraperitonial injection of LPS.2,3 This is likely due to the lack of mature IL-18 in these mice, since protection from LPS-induced lethality is not observed in IL
