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We have identified overexpression of the <jats:italic>cyclooxygenase-2<\/jats:italic> (<jats:italic>COX-2<\/jats:italic>) gene in NP tissues of Taiwanese CRSwNP patients. Therefore, in this study, we sought to investigate its protein expression\/location\/distribution in NP specimens and explore its roles in nasal polyposis. The COX-2 protein and mRNA expression was found higher in NPs than that in the control and CRSsNP patients\u2019 nasal tissues, mainly located at the epithelium and subepithelial stroma. Consistently, the CRS-related peptidoglycan (PGN) and bradykinin provoked COX-2 mRNA and protein upregulation in the human NP-derived fibroblasts and caused PGE<jats:sub>2<\/jats:sub>, thromboxane A<jats:sub>2<\/jats:sub> (TXA<jats:sub>2<\/jats:sub>), and interleukin (IL-6) secretion in culture medium. Further analysis revealed that the PI3K\/Akt activation and COX-2 induction were necessarily required for PGN-induced IL-6 production\/secretion and the induced PGE<jats:sub>2<\/jats:sub>, but not TXA<jats:sub>2<\/jats:sub>, was speculated to affect IL-6 protein trafficking and production. Finally, the IL-6 increase observed in vitro could also be detected in NP tissues. Collectively, we demonstrated here that COX-2 protein and IL-6 are overexpressed in human NP tissues. In response to PGN challenge, the PI3K\/Akt activation and COX-2-mediated PGE<jats:sub>2<\/jats:sub> autacoid correlates with extracellular IL-6 protein trafficking\/production in NP-derived fibroblasts, which can additionally contribute to the production of Th17-related cytokines such as IL-17 and TNF-\u03b1. This study also suggests COX-2 as a special biomarker for CRSwNP endotyping and may highlight the importance of COX-2 inhibitors in treating CRSwNP.<\/jats:p>","DOI":"10.1038\/s41598-024-58143-2","type":"journal-article","created":{"date-parts":[[2024,3,30]],"date-time":"2024-03-30T10:01:47Z","timestamp":1711792907000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The cyclooxygenase-2 upregulation mediates production of PGE2 autacoid to positively regulate interleukin-6 secretion in chronic rhinosinusitis with nasal polyps and polyp-derived fibroblasts"],"prefix":"10.1038","volume":"14","author":[{"given":"Jiunn-Min","family":"Shieh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yih-Jeng","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Chieh","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Li","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Bin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,30]]},"reference":[{"key":"58143_CR1","doi-asserted-by":"publisher","first-page":"1805","DOI":"10.1080\/14656566.2018.1527904","volume":"19","author":"UC Kucuksezer","year":"2018","unstructured":"Kucuksezer, U. 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