{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T05:53:12Z","timestamp":1792389192335,"version":"4.4.0"},"reference-count":58,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Innate Immun"],"abstract":"<jats:p>Introduction: Bothrops jararacussu venom contains snake venom metalloproteinases (SVMPs) that contribute to inflammation and tissue damage. BjussuMP-II, a PI class SVMP, lacks hemorrhagic activity but retains proteolytic and immunomodulatory properties. Methods: Here, we uncover a previously unrecognized function of BjussuMP-II in triggering NLRP3 inflammasome activation in human neutrophils, leading to IL-1\u03b2 release and pyroptosis. Inflammasome activation was investigated through gene expression analysis by quantitative PCR and protein expression by immunoblotting. Caspase-1 activation and gasdermin D (GSDMD) cleavage were assessed to confirm pyroptotic signaling. Pharmacological inhibition assays were performed to dissect the involvement of specific signaling pathways, and IL-1\u03b2 secretion was quantified by enzyme immunoassay. This discovery reveals a direct molecular link between SVMP activity and inflammasome-mediated inflammation, a fundamental mechanism with implications beyond snakebite pathology. It highlights inflammasomes as potential therapeutic targets to mitigate severe inflammatory responses in envenomed patients. Results: Mechanistically, BjussuMP-II increased expression of NLRP3, ASC, caspase-1, NEK7, and HIF-1\u03b1, as well as IL-1\u03b2 and GSDMD cleavage, confirmed by immunoblotting and immunofluorescence. It promoted the release of IL-1\u03b2, LTB&lt;sub&gt;4&lt;\/sub&gt;, LDH, and dsDNA, consistent with pyroptosis, and this release was reduced by MCC950 or disulfiram. Studies in Gsdmd\u2212\/\u2212 and HIF-1\u03b1-deficient neutrophils further demonstrated the requirement of these pathways for cytokine release. Conclusion: Collectively, these results indicate that BjussuMP-II modulates inflammasome-associated signaling pathways in neutrophils, contributing to the inflammatory responses triggered by SVMPs.<\/jats:p>","DOI":"10.1159\/000551301","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T17:05:09Z","timestamp":1772557509000},"page":"169-187","source":"Crossref","is-referenced-by-count":3,"title":["Neutrophil Inflammasome Activation and Pyroptosis Induced by a Metalloproteinase via HIF-1\u03b1 and Gasdermin D Pathways"],"prefix":"10.1159","volume":"18","author":[{"given":"Milena Daniela Souza","family":"Silva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina Pereira","family":"da Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa Ferreira","family":"de 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