{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T13:08:55Z","timestamp":1773839335255,"version":"3.50.1"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,6,29]],"date-time":"2016-06-29T00:00:00Z","timestamp":1467158400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Grant-in-Aid for Young Scientists (B)","award":["26861812"],"award-info":[{"award-number":["26861812"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Oral Diseases"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Diabetes is often associated with increased prevalence and severity of periodontal disease. We hypothesized that gingival epithelial cells modify periodontal disease progression and predicted that hyperglycemia would activate an inflammatory response in human gingival epithelial cells (<jats:styled-content style=\"fixed-case\">HGEC<\/jats:styled-content>s).<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>We tested our hypothesis in immortalized <jats:styled-content style=\"fixed-case\">HGEC<\/jats:styled-content>s (epi 4 cells) isolated from periodontal tissue and transfected with the simian virus 40 T antigen. The epi 4 cells were cultured in high (25\u00a0mM, <jats:styled-content style=\"fixed-case\">HG<\/jats:styled-content>) and normal (6\u00a0mM, <jats:styled-content style=\"fixed-case\">NG<\/jats:styled-content>) glucose conditions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The epi 4 cells showed increased interleukin\u20108 (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20108) protein secretion and <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> expression when cultured in <jats:styled-content style=\"fixed-case\">HG<\/jats:styled-content>, compared with in <jats:styled-content style=\"fixed-case\">NG<\/jats:styled-content>. These effects were not associated with increased cell proliferation and were not observed in a hyperosmolar control group (normal glucose with 19\u00a0mM mannitol). Increased <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20108 secretion in <jats:styled-content style=\"fixed-case\">HG<\/jats:styled-content> was inhibited by pretreatment with an antioxidant, N\u2010acetylcysteine, or a protein kinase C inhibitor, Ro31\u20108220. Hyperglycemia did not affect <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20108 secretion by gingival fibroblasts or periodontal ligament cells. In epi 4 cells, hyperglycemia also induced expression of toll\u2010like receptor 2 (<jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>2) but not <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings suggest a potential participation of epithelial cells in periodontal disease during diabetes by evoking an excessive host inflammatory response.<\/jats:p><\/jats:sec>","DOI":"10.1111\/odi.12502","type":"journal-article","created":{"date-parts":[[2016,5,12]],"date-time":"2016-05-12T15:33:58Z","timestamp":1463067238000},"page":"578-584","source":"Crossref","is-referenced-by-count":28,"title":["High glucose\u2010induced oxidative stress increases <scp>IL<\/scp>\u20108 production in human gingival epithelial cells"],"prefix":"10.1111","volume":"22","author":[{"given":"Y","family":"Kashiwagi","sequence":"first","affiliation":[{"name":"Division of Oral Biology and Disease 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