Glial cells are important players in the immune response in the CNS (Farina et al., 2007). Our previous studies demonstrated that ethanol activates TLR4 signaling in astrocytes (Blanco et al., 2005; Alfonso-Loeches et al., 2010). We therefore wondered if ethanol was also capable of activating the inflammasome in astroglial cells to contribute to ethanol-induced neuroinflammation. To answer this question, we first evaluated whether ethanol treatment promotes caspase-1 activation and the release of interleukins IL-1β and IL-18 in both cerebral cortex (Ctx) area (Figure 1E) and in cortical astroglial cells (Figure 2C). The biochemical and immunohistochemical analyses revealed that chronic ethanol treatment increases the co-localization of caspase-1 with GFAP-positive cells (Figures 1B,G) and up-regulates the total caspase-1 activity levels (Figure 1H) in the cerebral Ctx of WT mice when compared with untreated animals (Figures 1A,G). We also determined interleukins IL-1β and IL-18 in the Ctx of the WT and TLR4-KO mice treated with or without ethanol for 5 months. Figures 1I,J shows that ethanol treatment up-regulates the levels of IL-1β and IL-18 in the Ctx of the WT mice. Conversely, the
