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Here, we found that perturbation of ER\u2010Golgi trafficking by brefeldin A (BFA) treatment attenuated nucleotide\u2010binding oligomerization domain\u2010like receptor family, pyrin\u2013domain\u2013containing 3 (NLRP3) inflammasome activation in mouse bone marrow\u2013derived macrophages (BMDMs). BFA treatment inhibited NLRP3\u2010mediated inflammasome assembly and caspase\u20101 activation but did not block IL\u20101\u03b2 secretion from BMDMs following BFA administration after NLRP3 inflammasome activation. Consistently, short\u2010hairpin RNA\u2013dependent knockdown of BFA\u2010inhibited guanine nucleotide\u2010exchange protein 1 (BIG1), a molecular target of BFA and an initiator of Golgi\u2010specific vesicle trafficking, abolished NLRP3\u2010dependent apoptosis\u2010associated speck\u2010like protein containing a caspase\u2010recruitment domain oligomerization and caspase\u20101 activation in BMDMs. Similarly, knockdown of Golgi\u2010specific BFA\u2010resistance guanine nucleotide exchange factor 1, another target of BFA, clearly attenuated NLRP3\u2010mediated caspase\u20101 activation in BMDMs. Mechanistically, inhibition of BIGl\u2010mediated vesicle trafficking did not impair NLRP3\u2010activating signal 2\u2010promoted events, such as potassium efflux and mitochondrial rearrangement, but caused significant impairment of signal 1\u2010triggered priming steps, including NF\u2010\u03baB\u2013mediated pathways. These data suggest that BFA\u2010targeted vesicle trafficking at the Golgi contributes to activation of the NLRP3 inflammasome signaling.\u2014Hong, S., Hwang, I., Gim, E., Yang, J., Park, S., Yoon, S.\u2010H., Lee, W.\u2010W., Yu, J.\u2010W. Brefeldin A\u2013sensitive ER\u2010Golgi vesicle trafficking contributes to NLRP3\u2010dependent caspase\u20101 activation. FASEB J. 33, 4547\u20134558 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201801585r","type":"journal-article","created":{"date-parts":[[2018,12,28]],"date-time":"2018-12-28T14:05:33Z","timestamp":1546005933000},"page":"4547-4558","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Brefeldin A\u2013sensitive ER\u2010Golgi vesicle trafficking contributes to NLRP3\u2010dependent caspase\u20101 activation"],"prefix":"10.1096","volume":"33","author":[{"given":"Sujeong","family":"Hong","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology Institute for Immunology and Immunological Diseases Brain Korea 21 Program for Leading Universities and Students (PLUS) Project for Medical Science Yonsei University College of Medicine  Seoul 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