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Chunk #39 — RESULTS — ETHANOL-INDUCED MITOCHONDRIAL ROS FORMATION TRIGGERS NLRP3 INFLAMMASOME COMPLEX ACTIVATION

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Role of mitochondria ROS generation in ethanol-induced NLRP3 inflammasome activation and cell death in astroglial cells.
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ethanol (10 mM or 50 mM) markedly induced mROS production (Figure 4A). Notably, the mROS production induced by ethanol (10 and 50 mM) or LPS or ATP was significantly abrogated by Mito-TEMPO, z-YVAD-FMK, or Z-VAD-FMK by the presence of NLRP3 bp (Figure 4A). Strikingly, small, but non-significant, changes were noted in the TLR4-KO astrocytes incubated with ATP, or LPS or ethanol (Figure 4B). These results suggest that mROS generation induced by ATP or LPS or ethanol mediates NLRP3/caspase-1 inflammasome activation. Our findings also suggest crosstalk between TLR4 and NLRP3 inflammasome.