NLRP3 Inflammasome and Inflammatory Diseases

Abstract

Almost all human diseases are strongly associated with inflammation, and a deep understanding of the exact mechanism is helpful for treatment. The NLRP3 inflammasome composed of the NLRP3 protein, procaspase-1, and ASC plays a vital role in regulating inflammation. In this review, NLRP3 regulation and activation, its proinflammatory role in inflammatory diseases, interactions with autophagy, and targeted therapeutic approaches in inflammatory diseases will be summarized.

Figure 1

NLRP3 inflammasome-mediated inflammation and autophagy have complex and bidirectional regulatory effects. After being stimulated by Ca²⁺, K⁺, or ROS, the NLRP3 inflammasome is activated and recruits and activates procaspase-1 to generate active caspase-1, which then converts the cytokine precursor pro-IL-1β or other proinflammatory cytokines into mature and biologically active forms and triggers a series of inflammatory responses and pyroptotic cell death. However, this process can be regulated and interrupted by autophagy via damage of NLRP3 inflammasome; however, NLRP3 can promote cell autophagy via activation of the G-protein RalB. Interestingly, the relationship between NLRP3 and autophagy is not definitively understood, and there have also been reports that contradict the above statement such as NF-κB activation can modulate the NLRP3 and autophagy in same direction.