{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T16:22:05Z","timestamp":1785255725012,"version":"3.55.0"},"reference-count":68,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001184","name":"Cure Cancer Australia Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001184","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["2024\/GNT2038792"],"award-info":[{"award-number":["2024\/GNT2038792"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005923","name":"International Association for the Study of Lung Cancer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005923","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Acute pancreatitis (AP) is a multifactorial upper gastrointestinal inflammatory disorder that in severe cases (~20% of all AP) is associated with substantial morbidity and mortality, the latter coincident with multiorgan dysfunction, particularly acute lung injury (ALI). Currently, there are no effective therapeutic agents to treat AP\u2010induced ALI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      The expression and function of the protease A Disintegrin and Metalloproteinase 17 (ADAM17) were investigated in two murine models of AP\u2010associated ALI induced by L\u2010arginine or cerulein (ceruletide). A human lung\/pancreatic organoids co\u2010culture model of AP\u2010associated ALI was employed to validate ADAM17 up\u2010regulation\n                      <jats:italic>in vitro<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      ADAM17 expression was up\u2010regulated in pancreatic and lung tissues of wild\u2010type (WT) mice exposed to AP\u2010associated ALI models. The genetic (\n                      <jats:italic>Adam17<\/jats:italic>\n                      <jats:sup>ex\/ex<\/jats:sup>\n                      mice) and therapeutic (antisense oligonucleotides; ASOs) targeting of ADAM17 to reduce its expression in the lungs of mice ameliorated experimentally induced AP\u2010associated lung inflammation, which coincided with the selective reduction in the extracellular shedding of two ADAM17 substrates, soluble tumour necrosis factor \u03b1 (TNF\u03b1) and soluble interleukin\u20106 receptor (sIL\u20106R). ADAM17 targeting in AP\u2010associated ALI also suppressed lung inflammatory cell infiltration, including macrophages, as well as cellular death in the lung alveolar compartment. Furthermore, ADAM17 expression was up\u2010regulated by L\u2010arginine or cerulein (ceruletide) in an\n                      <jats:italic>in vitro<\/jats:italic>\n                      human lung\/pancreatic organoids co\u2010culture model of AP\u2010associated ALI.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>Our findings indicate that the ADAM17 protease plays a crucial role in the pathogenesis of acute lung inflammatory responses during AP progression, which could pave the way for devising novel therapeutic options to treat AP\u2010induced ALI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70443","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T05:16:27Z","timestamp":1776921387000},"page":"4126-4144","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The metalloproteinase ADAM17 promotes acute lung inflammatory responses during pancreatitis"],"prefix":"10.1111","volume":"183","author":[{"given":"Shermin","family":"Chan","sequence":"first","affiliation":[{"name":"South Australian immunoGENomics Cancer Institute (SAiGENCI) Adelaide University  Adelaide SA Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Hon","sequence":"additional","affiliation":[{"name":"South Australian immunoGENomics Cancer Institute (SAiGENCI) Adelaide University  Adelaide SA Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruby E.","family":"Dawson","sequence":"additional","affiliation":[{"name":"South Australian immunoGENomics Cancer Institute (SAiGENCI) Adelaide University  Adelaide SA Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Weng","sequence":"additional","affiliation":[{"name":"Centre for Innate Immunity and Infectious Diseases Hudson Institute of Medical Research  Clayton VIC Australia"},{"name":"Department of Molecular and Translational Sciences, Faculty of Medicine, Nursing and Health Sciences Monash University  Clayton VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Solujic","sequence":"additional","affiliation":[{"name":"Department of Thoracic Medicine Royal Adelaide Hospital  Adelaide SA Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7553-5163","authenticated-orcid":false,"given":"Yu C. 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Toby","family":"Coates","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Health Adelaide University  Adelaide SA Australia"},{"name":"Central and Northern Adelaide Renal and Transplantation Service Royal Adelaide Hospital  Adelaide SA Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Drogemuller","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Health Adelaide University  Adelaide SA Australia"},{"name":"Central and Northern Adelaide Renal and Transplantation Service Royal Adelaide Hospital  Adelaide SA Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eddie","family":"Sanderlin","sequence":"additional","affiliation":[{"name":"Ionis Pharmaceuticals  Carlsbad California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"Huang","sequence":"additional","affiliation":[{"name":"Ionis Pharmaceuticals  Carlsbad California 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