Cathepsin B Is Required for NLRP3 Inflammasome Activation in Macrophages, Through NLRP3 Interaction.

The mechanisms leading to NOD-leucine rich repeat and pyrin containing protein 3 (NLRP3) inflammasome activation are still debated. It is well established that oligomerized NLRP3 interacts with apoptosis associated Speck-like protein containing a CARD domain (ASC) which polymerizes into filaments recruiting procaspase-1, leading to its activation. However, pathways triggering NLRP3 activation, such as potassium efflux, ROS production or lysosomal permeabilization, can be required or not, depending on the activators used.

Heat Shock Proteins and Inflammasomes.

Heat shock proteins (HSP) regulate inflammation in many physiological contexts. However, inflammation is a broad process, involving numerous cytokines produced by different molecular pathways with multiple functions. In this review, we focused on the particular role of HSP on the inflammasomes intracellular platforms activated by danger signals and that enable activation of inflammatory caspases, mainly caspase-1, leading to the production of the pro-inflammatory cytokine IL-1β.

HSP70 is a negative regulator of NLRP3 inflammasome activation.

The NOD-leucine rich repeat and pyrin containing protein 3 (NLRP3) inflammasome is a multi-protein complex, aimed at producing IL-1β in response to danger signals which must be tightly regulated. Here we investigated the importance of the stress sensor, Heat Shock Protein 70 (HSP70) on NLRP3 inflammasome activation. HSP70 deficiency leads to the worsening of NLRP3-dependent peritonitis in mice.