The TLR4/TRIF-Mediated Activation of NLRP3 Inflammasome Underlies Endotoxin-Induced Liver Injury in Mice

Figure 7

Molecular and cellular mechanisms for LPS phase. After challenge of P. acnes-primed wild-type mice with LPS, TLR4 is activated via TRIF for activation of NLRP3 inflammasome, which eventually leads to cleavage of procaspase-1 into its active form caspase-1. Active caspase-1, then, processes pro-IL-18 into active IL-18 for extracellular release. IL-18 upregulates both hepatotoxic Fas ligand (FasL) expression and TNF-𝛼 production. DAMPs and alarmin released from the injured hepatocytes might further activate the Kupffer cells, eventually resulting in the acceleration of inflammatory responses. DAMPs, damage-associated molecular patterns.