Theoredoxin oxidation mediated by mitochondrial ROS is a key event in NLRP3 inflammasome activation.

Abstract

The involvement of reactive oxygen species (ROS) in the NLRP3 inflammasome activation has sparked a lot of controversy in literature. This controversy can be explained by the usage of different experimental setup conditions due to the differing redox states of the most commonly used cell types. Mitochondria, ROS and the antioxidant response are key players in the activation cascade of the NLRP3 inflammasome. Thioredoxin (TRX) is of paramount importance in the regulation of the NLRP3 inflammasome and regulates the pro-IL-1β production as well as the activation of the inflammasome. Finally its reducing capacities also enable it to regulate the activity of caspase-1 by reducing oxidized cysteine residues. Literature data has been compiled to proposed a model for NLRP3 inflammasome activation in response to adinosinetriphosphate (ATP) and lipopolysaccaride (LPS). In this model the central role of TRX oxidation links mitochondrial ROS with the activation of the NLRP3 inflammasome. Finally this model has been used to better understand NLRP3-inflammasome-associated diseases. With this understanding several novel potential disease-causing genes have been identified.