PX-12 Inhibits NLRP3 Inflammasome Activation to Treat Psoriasis

The study demonstrates that 1-methylpropyl 2-imidazolyl disulfide (PX-12) has potential inhibitory effects on imiquimod (IMQ)-induced IL-1β and IL-18 secretion, as well as pyroptotic cell death in lipopolysaccharide (LPS)-primed THP-1 macrophages. PX-12 also inhibited the release of IL-1β, IL-18, and pyroptotic LDH in nigericin- and monosodium urate-stimulated macrophages. It reduced intracellular reactive oxygen species generation and caspase-1 activation in IMQ-induced THP-1 macrophages, suggesting that ROS, potassium, and lysosome damage are associated with the mechanisms of PX-12. Furthermore, PX-12 ameliorated IMQ-induced psoriasis-like skin symptoms in mice. Therefore, PX-12 acts as an inhibitor of NLRP3 inflammasome and has the potential to treat psoriasis.