{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T16:51:28Z","timestamp":1792083088195,"version":"4.4.0"},"reference-count":25,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:00:00Z","timestamp":1789171200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:00:00Z","timestamp":1789171200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Dig Dis"],"abstract":"<jats:p>Introduction: Chronic pancreatitis (CP) is a fibro-inflammatory syndrome characterized by irreversible tissue damage leading to exocrine and endocrine insufficiency, persistent pain, and an increased risk of pancreatic cancer. This study investigates the role of IL-18 in the activation process of pancreatic stellate cells (PSCs) and the progression of pancreatic fibrosis in CP. Methods: A total of 69 CP and 32 normal pancreatic tissue samples were analyzed using qRT-PCR and IHC to assess IL-18R1 expression. Primary PSCs were isolated from murine pancreata and cultured. Effects of recombinant IL-18 on PSC activation were evaluated using qRT-PCR and flow cytometry. Additionally, the impact of IL-18 binding protein (IL-18BP) and IL-18R1 antibody on PSC activation was examined. Results: IL-18R1 expression was significantly upregulated in CP tissues compared to normal pancreatic tissues, correlating with fibrosis severity. Cultured PSCs showed increased \u03b1-SMA and IL-18R1 expression over time, indicating activation. Treatment with recombinant IL-18 induced a dose-dependent increase in \u03b1-SMA expression, confirming PSC activation. Furthermore, cultured PSCs secreted IL-18, suggesting an autocrine activation mechanism. IL-18BP and IL-18R1 antibody treatments reduced PSC activation, underscoring IL-18\u2019s regulatory role. Conclusion: Upregulation of IL-18R1 and its correlation with fibrosis severity in CP highlights the significant role of IL-18 in PSC activation and pancreatic fibrosis. These findings suggest that targeting the IL-18\/IL-18R1 axis could be a promising therapeutic strategy to mitigate pancreatic fibrosis in CP, offering potential new avenues for treatment.<\/jats:p>","DOI":"10.1159\/ddi\/acnag004","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T11:50:23Z","timestamp":1789127423000},"page":"1-1","source":"Crossref","is-referenced-by-count":0,"title":["IL-18\/IL-18R1 Involved in Pancreatic Fibrosis via Activating Pancreatic Stellate Cells"],"prefix":"10.1159","author":[{"given":"Ughur","family":"Aghamaliyev","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Sirtl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Munker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"Weniger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip Z.","family":"Brohawn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Banu","family":"Astanova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00fcralp O.","family":"Ceyhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merve","family":"Bozkurt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"Friess","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7813-2482","authenticated-orcid":false,"given":"Jens","family":"Werner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandr","family":"Bazhin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan G.","family":"D\u2019Haese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Ilmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9574-8051","authenticated-orcid":false,"given":"Bernhard W.","family":"Renz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2026,9,12]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199506013322206"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2011.328"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.07.066"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2009.07.038"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2011-301220"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2021.112634"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ircmb.2022.10.004"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.09.040"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1097\/MPA.0000000000000928"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.354"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2019.11.001"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2006.105528"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1136\/gut.43.1.128"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1136\/gut.44.4.534"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00388.2014"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5297.206"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v12.i40.6507"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00210.2017"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1601350"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehx261"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00564-2015"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1084\/jem.187.12.2103"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2018-317098"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1038\/77811"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20030649"}],"container-title":["Digestive Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/article-pdf\/doi\/10.1159\/ddi\/acnag004","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T16:03:44Z","timestamp":1792080224000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/ddi\/acnag004"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,12]]},"references-count":25,"URL":"https:\/\/doi.org\/10.1159\/ddi\/acnag004","archive":["Portico"],"relation":{},"ISSN":["0257-2753","1421-9875"],"issn-type":[{"value":"0257-2753","type":"print"},{"value":"1421-9875","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,12]]}}}