Innate immune activation can occur in the nervous system in response to infections and/or tissue damage (Lampron et al., 2013). Two main receptors and signaling pathways are involved in this response, membrane receptors TLRs and cytoplasm sensors NLRPs, which regulate caspase-1 activity through inflammasome formation. Activation of TLRs has been shown to participate in brain infection and neurodegenerative disorders (Hanamsagar et al., 2012). However, less information is available on the role of inflammasome in brain damage and neuroinflammation, and the cellular source of inflammasome activation during brain infection or injury is lacking. In this study, we show that astrocytes express various inflammasomes, although NRLP3 expression is higher. We further demonstrate that ethanol as well as ATP or LPS, triggers the recruitment of NLRP3 and active caspase-1 within mitochondria by inducing mROS formation, which promotes the production of IL-1β and IL-18. The present findings also reveal crosstalk between TLR4 and the NLRP3 inflammasome complex since the elimination of the TLR4 function markedly reduces ethanol- or ATP-induced NLRP3 inflammasome activation and cytokines production.
