{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T13:59:24Z","timestamp":1754488764615,"version":"3.41.2"},"reference-count":51,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,6,6]],"date-time":"2022-06-06T00:00:00Z","timestamp":1654473600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Helicobacter"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>Helicobacter bilis<\/jats:italic>, an enterohepatic <jats:italic>Helicobacter<\/jats:italic> species, represents a carcinogenic risk factor for cholangiocytes owing to the prevalence of infections in patients with biliary tract cancer, cholecystitis, and pancreaticobiliary maljunction. However, the effect of <jats:italic>H.\u00a0bilis<\/jats:italic> infection on cholangiocytes and the process and mechanism of carcinogenesis are not known. We aimed to determine the effects of <jats:italic>H.\u00a0bilis<\/jats:italic> on cholangiocytes, focusing on inflammation and oxidative stress.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p><jats:italic>Helicobacter bilis<\/jats:italic> and MMNK\u20101 cells were cocultured for 24\u2009h and inflammatory cytokine secretion was evaluated. Furthermore, MMNK\u20101 cell proliferation, intracellular reactive oxidant species (ROS) production, and DNA damage caused by ROS were investigated. All factors were compared with and without <jats:italic>H.\u00a0bilis<\/jats:italic> infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Interleukin (IL)\u20106 and IL\u20108 secretion were significantly increased in MMNK\u20101 cocultures with <jats:italic>H.\u00a0bilis<\/jats:italic> (IL\u20106, 24.3\u2009\u00b1\u200912.2 vs. 271.1\u2009\u00b1\u2009286.4\u00a0pg\/ml; IL\u20108, 167.6\u2009\u00b1\u200978.7 vs. 1085.1\u2009\u00b1\u20091047.1\u2009pg\/ml, <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05). MMNK\u20101 proliferation was also significantly higher in <jats:italic>H.\u00a0bilis<\/jats:italic> cocultures (1.05\u2009\u00b1\u20090.02 vs. 1.00\u2010fold, respectively; <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05). Coculturing enhanced the production of ROS in MMNK\u20101 cells depending on the cell concentration of <jats:italic>H.\u00a0bilis<\/jats:italic> (1.0 vs. 1.17\u2009\u00b1\u20090.06, <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05); however, DNA injury was not observed in cocultures with <jats:italic>H.\u00a0bilis<\/jats:italic> (5.35\u2009\u00b1\u20090.87 vs. 6.08\u2009\u00b1\u20090.55\u2009pg\/\u03bcl, <jats:italic>p<\/jats:italic>\u00a0=\u00a0.06).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p><jats:italic>Helicobacter bilis<\/jats:italic> infection induced ROS production in and enhanced the proliferation of cholangiocytes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hel.12908","type":"journal-article","created":{"date-parts":[[2022,6,6]],"date-time":"2022-06-06T12:15:36Z","timestamp":1654517736000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["<i>Helicobacter bilis<\/i> infection 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