{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T10:55:07Z","timestamp":1778756107660,"version":"3.51.4"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,3,26]],"date-time":"2016-03-26T00:00:00Z","timestamp":1458950400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["25893127"],"award-info":[{"award-number":["25893127"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["25862046"],"award-info":[{"award-number":["25862046"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:sec><jats:title>Background and Objective<\/jats:title><jats:p>Hypoxia has been widely studied in inflammatory diseases as it can modulate the inflammatory response, mainly via the hypoxia\u2010inducible factor (<jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>). However, little is known about the effects of hypoxia and the role of <jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content> in the inflammatory responses to periodontitis.<\/jats:p><jats:p>In this study, we focused on the gingival epithelium that is exposed to relatively low levels of oxygen. We investigated whether hypoxic conditions have an impact on inflammatory responses in human gingival epithelial cells (<jats:styled-content style=\"fixed-case\">HGEC<\/jats:styled-content>s).<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and Methods<\/jats:title><jats:p>Pimonidazole <jats:styled-content style=\"fixed-case\">HC<\/jats:styled-content>l, which accumulates in hypoxic cells, was administered intraperitoneally to C57<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>\/6 mice with or without <jats:italic>Porphyromonas gingivalis<\/jats:italic> infection. Immunohistochemistry was then performed to detect the hypoxic cells in periodontal tissue. Immortalized <jats:styled-content style=\"fixed-case\">HGEC<\/jats:styled-content>s were cultured under hypoxic conditions with or without interleukin (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>)\u20101\u03b2, and the expression levels of <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106 and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20108 were measured by real\u2010time reverse transcription\u2013polymerase chain reaction and enzyme\u2010linked immunosorbent assay. <jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>\u20101\u03b1 expression was detected by western blotting. The <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\u2010binding activity of <jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>\u20101\u03b1 was determined by a <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\u2010binding enzyme\u2010linked immunosorbent assay. The involvement of <jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>\u20101\u03b1 in the hypoxic response was examined by transfection with <jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>\u20101\u03b1 si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Immunohistochemistry revealed pimonidazole <jats:styled-content style=\"fixed-case\">HC<\/jats:styled-content>l accumulation in the gingival epithelium of both normal and <jats:italic>P. gingivalis<\/jats:italic>\u2010infected mice, with a slightly stronger signal in the <jats:italic>P. gingivalis<\/jats:italic>\u2010infected mice than in the normal mice. The <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u03b2\u2010induced <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106 and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20108 production by <jats:styled-content style=\"fixed-case\">HGEC<\/jats:styled-content>s was suppressed under hypoxic conditions. <jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>\u20101\u03b1 accumulated during hypoxia, and this accumulation was further enhanced by <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u03b2 treatment. The hypoxia\u2010dependent suppression of <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106 and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20108 expression was reversed by treating the cells with <jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>\u20101\u03b1 si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results suggest that the gingival epithelium is exposed to low oxygen tension in periodontal tissue and that this hypoxic condition modulates the local inflammatory response of gingival epithelial cells in an <jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>\u20101\u03b1\u2010dependent manner.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jre.12377","type":"journal-article","created":{"date-parts":[[2016,3,26]],"date-time":"2016-03-26T14:40:28Z","timestamp":1459003228000},"page":"127-134","source":"Crossref","is-referenced-by-count":17,"title":["Hypoxia\u2010inducible factor\u20101\u03b1 inhibits interleukin\u20106 and \u20108 production in gingival epithelial cells during hypoxia"],"prefix":"10.1111","volume":"52","author":[{"given":"M.","family":"Takedachi","sequence":"first","affiliation":[{"name":"Department of Periodontology Osaka University Graduate School of Dentistry Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Iyama","sequence":"additional","affiliation":[{"name":"Department of Periodontology Osaka University Graduate School of Dentistry Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Sawada","sequence":"additional","affiliation":[{"name":"Department of Periodontology Osaka 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