Fig. 8: A schematic view of high-dose propofol induced mitochondrial apoptosis and caspase-1-dependent pyroptosis in macrophages.

NLRP3 activation and secondary pyroptosis induce cell death after propofol exposure, as shown by cleaved-caspase-1 and cleaved IL-1β. When NLRP3 is knocked out, we speculate that the AIM2 inflammasome induces caspase-1-dependent pyroptosis. Propofol activates the proprotein form of caspase-1 in an inflammasome adaptor ASC-mediated manner via the NLRP3 and AIM2 inflammasomes. We speculate that propofol-induced mitochondrial ROS trigger NLRP3 inflammasome activation. Simultaneously, propofol also involves in the mitochondria-associated apoptosis in macrophages. Knockout of caspase-1 did not block macrophage cytotoxicity, and macrophages lacking caspase-1 are susceptible to propofol-induced apoptosis. We have provided an explanation: activation of NLRP3 is necessary and sufficient for pyroptosis in propofol-induced cell death. Both apoptotic and pyroptotic cellular death pathways were activated after propofol exposure. Thus, further uncovering the cross talk between pyroptosis and mitochondrial apoptosis will increase our understanding of anaesthetic-induced cell death