Therefore, the lack of TLR4 function in TLR4-KO astrocytes not only eliminates the priming signal, as production of pro-IL-1β, but also the production of cytokines and free radicals-mediated by TLR4 signaling. These later events could, sensitize the mitochondria to induce ROS production and consequently NLRP3 activation and cell death by pyroptosis and apoptosis. Accordingly, recent evidence has demonstrated that TLR4 signaling induce mitochondria ROS production, contributing to the gastric cancer progression (Yuan et al., 2013). The functional role of TLR4 in the inflammasome activation is further supported by the demonstration that TLR4 deficiency not only protects ethanol-induced NLRP3 inflammasome activation and the induction of cytokines, but also attenuates the increased in ethanol-induced IL-1β production in the cerebellum (Lippai et al., 2013). We also noted that in vivo ethanol treatment abolishes the induction of IL-18 and IL-1β production in the cerebral cortex of TLR4-KO mice.
