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However, the molecular mechanisms underlying <jats:italic>T. serrulatus<\/jats:italic> venom (TsV) activity remain unknown. Here we show that TsV triggers NLRP3 inflammasome activation via K<jats:sup>+<\/jats:sup> efflux. Mechanistically, TsV triggers lung-resident cells to release PGE<jats:sub>2<\/jats:sub>, which induces IL-1\u03b2 production via E prostanoid receptor 2\/4-cAMP-PKA-NF\u03baB-dependent mechanisms. IL-1\u03b2\/IL-1R actions account for oedema and neutrophil recruitment to the lungs, leading to TsV-induced mortality. Inflammasome activation triggers LTB<jats:sub>4<\/jats:sub> production and further PGE<jats:sub>2<\/jats:sub> via IL-1\u03b2\/IL-1R signalling. Activation of LTB<jats:sub>4<\/jats:sub>-BLT1\/2 pathway decreases cAMP generation, controlling TsV-induced inflammation. Exogenous administration confirms LTB<jats:sub>4<\/jats:sub> anti-inflammatory activity and abrogates TsV-induced mortality. These results suggest that the balance between LTB<jats:sub>4<\/jats:sub> and PGE<jats:sub>2<\/jats:sub> determines the amount of IL-1\u03b2 inflammasome-dependent release and the outcome of envenomation. We suggest COX1\/2 inhibition as an effective therapeutic intervention for scorpion envenomation.<\/jats:p>","DOI":"10.1038\/ncomms10760","type":"journal-article","created":{"date-parts":[[2016,2,23]],"date-time":"2016-02-23T15:55:13Z","timestamp":1456242913000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":109,"title":["Opposing roles of LTB4 and PGE2 in regulating the inflammasome-dependent scorpion venom-induced mortality"],"prefix":"10.1038","volume":"7","author":[{"given":"Karina F.","family":"Zoccal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos A.","family":"Sorgi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana I.","family":"Hori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco W. 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