{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T04:04:32Z","timestamp":1779681872292,"version":"3.53.1"},"reference-count":43,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20K07635"],"award-info":[{"award-number":["20K07635"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["B8F2025A01"],"award-info":[{"award-number":["B8F2025A01"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes to Cells"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Interleukin\u201018 (IL\u201018) is a pro\u2010inflammatory cytokine, and higher IL\u201018 expression in pancreatic tumors is associated with poor prognosis. Although 5\u2010fluorouracil (5\u2010FU) has been reported to induce the release of bioactive (mature\/cleaved) IL\u201018 from the pancreatic cancer cell line Capan\u20102, the underlying mechanism remains unclear. Here, we investigated IL\u201018 activation in pancreatic cancer cells after 5\u2010FU treatment under low\u2010nutrient conditions that mimic key features of the tumor microenvironment, using a monoclonal antibody we generated that specifically recognizes cleaved, active IL\u201018. We detected the release of active IL\u201018 from both Capan\u20102 and MIA PaCa\u20102 cells after 5\u2010FU treatment. Analysis of separated attached and detached cell fractions showed that IL\u201018 cleavage occurred predominantly in detached cells. We also clarified that caspase\u20108\u2014but not caspase\u20101\/4\u2014was activated in detached cells and was required for IL\u201018 and GSDMD cleavage that is a hallmark of pyroptosis. Surprisingly, detached cells from only nutrient starvation showed the same phenomenon, and 5\u2010FU contributed to increased pyroptotic cells. On the other hand, the release of active IL\u201018 was not observed with gemcitabine. These findings suggest that a low\u2010nutrient tumor microenvironment and 5\u2010FU therapy can promote caspase\u20108\u2013dependent pyroptotic cell death with IL\u201018 activation, potentially contributing to chronic inflammation in pancreatic tumors.<\/jats:p>","DOI":"10.1111\/gtc.70111","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T11:22:17Z","timestamp":1775474537000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Mechanism of Caspase\u20108\u2013Dependent Interleukin\u201018 Activation in Pancreatic Cancer Cells Induced by 5\u2010Fluorouracil and Nutrient Starvation"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2489-0453","authenticated-orcid":false,"given":"Hiroki","family":"Kamino","sequence":"first","affiliation":[{"name":"Center for Vaccines and Therapeutic Antibodies for Emerging Infectious Diseases Shimane University  Izumo Shimane Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Nariai","sequence":"additional","affiliation":[{"name":"Center for Vaccines and Therapeutic Antibodies for Emerging Infectious Diseases Shimane University  Izumo Shimane Japan"},{"name":"mAbProtein Co. Ltd  Izumo Shimane Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Urano","sequence":"additional","affiliation":[{"name":"Center for Vaccines and Therapeutic Antibodies for Emerging Infectious Diseases Shimane University  Izumo Shimane Japan"},{"name":"mAbProtein Co. Ltd  Izumo Shimane Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,6]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80596-8"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1202121"},{"key":"e_1_2_12_4_1","first-page":"1408","article-title":"The Unique Physiology of Solid Tumors: Opportunities (And Problems) for Cancer Therapy","volume":"58","author":"Brown J. 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