Caspase-1 is an enzyme involved in the conversion of interleukin-1 into its active secreted form. Interleukin-1 mediates inflammatory responses during infection and disease. Caspase-1 is recruited to and activated by the inflammasome complex (1). Under normal cellular conditions caspase-1 exists in an inactive pro form. Following stimulation with LPS or various microbial signals procaspase-1 is proteolytically cleaved into 10- and 20-kDa subunits that are enzymatically active (2). These cleavage products can be detected by western blot with the caspase-1 antibody to monitor activation. This strategy was used in a study of the innate immune recognition of the Shigella pathogen (3). The authors used the caspase-1 antibody to monitor activation of inflammation and detail the mechanism by which Shigella is able to evade detection by remodeling its LPS. In addition to the cleavage of interleukin-1, activation of caspase-1 is also important for the induction pyroptosis, a pro-inflammatory form of cell death typically induced in infected macrophages. This pathway is essential to sense and respond to pathogen-associated molecular patterns such as bacterial cell wall components or bacterial flagellin (4). Caspase-1 knockout mice develop normally and display normal apoptotic responses (1). This result indicates caspase-1 is not essential for canonical apoptotic pathways. However, recently caspase-1 has been shown to be involved in cell-death in response to injury or disease. For example, caspase-1 is involved in neuronal cell death following stroke or during neurodegenerative disease (1). These functions of caspase-1 were investigated in detail by Mawhinney et al. (5). Their study measured levels of inflammasome pathway components in young and old rats to look at the effect of inflammation on age-related cognitive decline. Using the caspase-1 antibody for western blotting and immunofluorescence, they found heightened levels in old rats that were correlated with cognitive deficits (5). Another study has demonstrated the role of neuroinflammation following injury as well. The Keane group at the University of Miami Miller School of Medicine examined pro-inflammatory signals following acute CNS trauma and looked at ways to block this response (6). Their work with the caspase-1 antibody showed increased caspase-1 levels and inflammation immediately following injury. Through the delivery of siRNA targeting the inflammasome the authors were able to successfully block caspase-1 activation. Along these same lines, Tomura et al. studied inflammation following traumatic brain injury in a neuronal cell culture model (7). Their study examined the effects of therapeutic hypothermia following brain injury specifically at the level of inflammatory response. Hypothermia reduced caspase-1 processing as demonstrated through western blotting and immunofluorescence with the caspase-1 antibody (7). This study suggests a potential mechanism to explain the effectiveness of therapeutic hypothermia following traumatic brain injury.
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