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After NLRP3 activation, it recruits the adaptor protein ASC (apoptosis\u2010associated speck\u2010like protein containing a CARD) and the effector protein caspase\u20101 (CASP\u20101) to form a multiprotein complex, which is named NLRP3 inflammasome, enables the cleavage of caspase\u20101. Furthermore, the active c\u2010caspase\u20101 proteolytically cleaves GSDMD into N\u2010GSDMD, which forms pores on the membrane, thus inducing the leakage of pro\u2010inflammatory cytokines, including IL\u20101\u03b2 and IL\u201018, which leads to lytic cell death, defined as pyroptosis. Recent studies suggest that the abnormal activation of NLRP3 inflammasome in human nasal epithelial cells, mucosal T lymphocytes, and mucosal macrophages is associated with the pathogenesis of chronic rhinosinusitis (CRS). However, the underlying mechanism is still unclear. To provide further perspective on how the NLRP3 inflammasome is activated in CRS, this review focuses on the structure\u2010derived assembly and activation of the NLRP3 inflammasome, and its roles and the potential activation mechanism in CRS. We also discuss major cellular stress signals that trigger the NLRP3 inflammasome.<\/jats:p>","DOI":"10.1002\/wjo2.70037","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T06:54:57Z","timestamp":1755500097000},"page":"362-373","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Mechanism of NLRP3 Inflammasome Activation and Its Roles in Chronic Rhinosinusitis"],"prefix":"10.1002","volume":"12","author":[{"given":"Dong\u2010Lin","family":"Li","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery The Third Affiliated Hospital of Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery The Third Affiliated Hospital of Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan\u2010Jie","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery The Third Affiliated Hospital of Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ge\u2010Hua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery The Third Affiliated Hospital of Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8668-1916","authenticated-orcid":false,"given":"Li\u2010Hong","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery The Third Affiliated Hospital of Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,17]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.12577"},{"issue":"29","key":"e_1_2_13_3_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4193\/Rhin20.600","article-title":"European Position Paper on Rhinosinusitis and Nasal Polyps 2020","volume":"58","author":"Fokkens W. 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