While known for their role in programmed cell death, caspases are also essential for mediating inflammatory responses and innate immunity. Binding of microbial molecules by pattern recognition receptors triggers the formation of the multiprotein inflammasome complex and the activation of caspase-1 (1). Caspase-1 is then able to mediate the activation and secretion of proinflammatory cytokines including interleukin-1. In addition to caspase-1, caspase-11 also plays an important role during the inflammatory response. Depending on the type of pathogen infection, casapse-11 is needed for caspase-1 activation and the processing of proinflammatory cytokines (1). This alternative pathway to inflammasome activation represents a noncanonical proinflammatory mechanism that is currently under investigation (1). Unlike other caspase family members, expression of caspase-11 is induced by inflammatory stimulation. Additionally, studies suggest expression of procaspase-11 is sufficient for its own auto-processing and activation (1). This is in contrast to other caspase family members which often require activation by upstream pathways. Other mechanisms for caspase-11 activation have been proposed, including the possibility of a yet undiscovered scaffold complex that promotes oligomerization and cleavage of procaspase-11 (1). Given the role of caspase-11 in the induction of inflammatory responses, more research is needed to identify mechanisms of caspase-11 activation as wells as its downstream substrates.
Caspase-11 activation has been investigated in response to stroke (2). Researchers from Harvard Medical School performed western blots with a caspase-11 antibody and showed caspase-11 was induced following ischemic brain injury and was needed for apoptosis (2). This study also used the caspase-11 antibody to monitor in vitro autoprocessing and identified caspase-3 as an additional target of active caspase-11 (2). In a related study Tomura et al. used caspase-11 antibody to show caspase-11 is induced following traumatic brain injury (3). The researchers showed hypothermic conditions prevented caspase-11 expression (3). This result suggests therapeutic hypothermia might protect the brain from injury by preventing cell death through the innate immune system (3). A study from Yale University School of Medicine identified a mechanism of caspase-1 activation independent from bacterial flagellin (4). Their study used caspase-11 antibody to show induction of cell death by Legionella infection required caspase-11 expression (4). By monitoring levels of procaspase-11 and caspase-11 through western blots with the caspase-11 antibody the researchers demonstrated LPS was able to induce caspase-11 activation in the absence of flagellin (4).