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• W2907314796 abstract "Endoplasmic reticulum (ER)-Golgi vesicle trafficking plays a pivotal role in the conventional secretory pathway of many cytokines; however, the precise release mechanism of a major inflammasome mediator, IL-1β, is not thought to follow the conventional ER-Golgi route and remains elusive. Here, we found that perturbation of ER-Golgi trafficking by brefeldin A (BFA) treatment attenuated nucleotide-binding oligomerization domain-like receptor family, pyrin-domain-containing 3 (NLRP3) inflammasome activation in mouse bone marrow-derived macrophages (BMDMs). BFA treatment inhibited NLRP3-mediated inflammasome assembly and caspase-1 activation but did not block IL-1β secretion from BMDMs following BFA administration after NLRP3 inflammasome activation. Consistently, short-hairpin RNA-dependent knockdown of BFA-inhibited guanine nucleotide-exchange protein 1 (BIG1), a molecular target of BFA and an initiator of Golgi-specific vesicle trafficking, abolished NLRP3-dependent apoptosis-associated speck-like protein containing a caspase-recruitment domain oligomerization and caspase-1 activation in BMDMs. Similarly, knockdown of Golgi-specific BFA-resistance guanine nucleotide exchange factor 1, another target of BFA, clearly attenuated NLRP3-mediated caspase-1 activation in BMDMs. Mechanistically, inhibition of BIG1-mediated vesicle trafficking did not impair NLRP3-activating signal 2-promoted events, such as potassium efflux and mitochondrial rearrangement, but caused significant impairment of signal 1-triggered priming steps, including NF-κB-mediated pathways. These data suggest that BFA-targeted vesicle trafficking at the Golgi contributes to activation of the NLRP3 inflammasome signaling.-Hong, S., Hwang, I., Gim, E., Yang, J., Park, S., Yoon, S.-H., Lee, W.-W., Yu, J.-W. Brefeldin A-sensitive ER-Golgi vesicle trafficking contributes to NLRP3-dependent caspase-1 activation." @default.
• W2907314796 created "2019-01-11" @default.
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• W2907314796 date "2018-12-28" @default.
• W2907314796 modified "2023-10-16" @default.
• W2907314796 title "Brefeldin A–sensitive ER‐Golgi vesicle trafficking contributes to NLRP3‐dependent caspase‐1 activation" @default.
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• W2907314796 doi "https://doi.org/10.1096/fj.201801585r" @default.
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