Inflammasome‐associated cell death: Pyroptosis, apoptosis, and physiological implications

Abstract Inflammasomes are innate immune mechanisms that promote inflammation by activating the protease caspase‐1. Active caspase‐1 induces pyroptosis, a necrotic form of regulated cell death, which facilitates the release of intracellular proinflammatory molecules, including IL‐1 family cytokines. Recent studies identified mediators of inflammasome‐associated cell death and suggested that inflammasomes induce not only pyroptosis, but also apoptosis. Caspase‐1 has the potential to induce pyroptosis and apoptosis in a manner that is dependent on the expression of the pyroptosis mediator gasdermin D. Caspase‐1‐induced apoptosis is mediated by Bid and caspase‐7. Caspase‐8 is also activated following the formation of inflammasomes and may induce apoptosis. Because inflammasomes contribute to the pathogenesis of inflammatory disorders and host defenses against microbial pathogens, a more detailed understanding of the mechanisms underlying inflammasome‐associated cell death may contribute to the development of novel therapeutic strategies for inflammasome‐related diseases. Pyroptosis has been implicated in inflammasome‐related diseases, and compounds that inhibit this process have been reported. The molecular mechanisms of inflammasome‐associated cell death and its physiological implications are discussed herein.