{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T20:42:22Z","timestamp":1789936942115,"version":"4.0.1"},"reference-count":38,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,10,6]],"date-time":"2015-10-06T00:00:00Z","timestamp":1444089600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007854","name":"School of Dentistry, Nihon University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007854","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007683","name":"Nihon University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007683","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:label\/><jats:p>Cigarette smoking is one of the most important risk factors for the development of various diseases. Nicotine is the most extensively investigated component of cigarette smoke, and a comprehensive analysis of the genes induced by nicotine stimulation revealed that interleukin\u20108 (IL\u20108) was induced in oral squamous cell carcinoma cell (OSCC). Based on this background, the signaling mechanisms of nicotine\u2010mediated IL\u20108 induction in OSCC was investigated. Augmented IL\u20108 secretion by Ca9\u201022 cells was blocked by the NF\u2010\u03baB inhibitor L\u20101\u20104\u2032\u2010tosylamino\u2010phenylethyl\u2010chloromethyl ketone (TPCK) and the nicotinic acetylcholine receptor (nAChR)\u2010specific inhibitor \u03b1\u2010bungarotoxin (\u03b1Btx). The downstream signaling pathway was further examined by pre\u2010incubating the cells with inhibitors against mitogen\u2010activated protein kinase (MEK), protein kinase C (PKC), and Ca<jats:sup>2+<\/jats:sup>\/calmodulin\u2010dependent kinase II (CaMK II). Only the CaMK II inhibitor was found to exert an inhibitory effect on nicotine\u2010mediated IL\u20108 secretion. Pre\u2010treatment of the Ca9\u201022 cells with the Ca<jats:sup>2+<\/jats:sup> chelator BAPTA\u2010AM drastically inhibited IL\u20108 secretion. Although nicotine stimulation induced the phosphorylation of the NF\u2010\u03baB p65 subunit, pre\u2010treatment with BAPTA\u2010AM was found to inhibit this activity significantly. CaMK II\u2010dependent p65 phosphorylation was confirmed by pre\u2010incubation of the cells with CaMK II inhibitor. The results from this study indicate that the binding of nicotine to nAChR induces Ca<jats:sup>2+<\/jats:sup> influx, which results in the activation and phosphorylation of CaMK II and NF\u2010\u03baB p65, respectively. Nicotine\u2010mediated IL\u20108 induction should be a trigger for the initiation of various diseases. J. Cell. Biochem. 117: 1009\u20131015, 2016. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcb.25387","type":"journal-article","created":{"date-parts":[[2015,9,29]],"date-time":"2015-09-29T12:36:26Z","timestamp":1443530186000},"page":"1009-1015","source":"Crossref","is-referenced-by-count":15,"title":["Nicotine\u2010Mediated Ca<sup>2+<\/sup>\u2010Influx Induces IL\u20108 Secretion in Oral Squamous Cell Carcinoma Cell"],"prefix":"10.1002","volume":"117","author":[{"given":"Kou","family":"Tsunoda","sequence":"first","affiliation":[{"name":"Division of Applied Oral Sciences Nihon University Graduate School of Dentistry Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ichiro","family":"Tsujino","sequence":"additional","affiliation":[{"name":"Division of Respiratory Medicine Nihon University School of Medicine Tokyo 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