{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T18:51:31Z","timestamp":1783104691226,"version":"3.54.6"},"reference-count":59,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T00:00:00Z","timestamp":1678838400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007190","name":"Unilever","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Objective<\/jats:title><jats:p>Plaque\u2010induced gingival inflammation (gingivitis) is ubiquitous in humans. The epithelial barrier reacts to the presence of oral bacteria and induces inflammatory cascades. The objective of this study was to investigate the mechanism by which the small molecule micronutrient curcumin could decrease inflammatory response in vitro to oral bacterium heat\u2010killed <jats:italic>Fusobacterium nucleatum<\/jats:italic> as curcumin could be a useful compound for combatting gingivitis already consumed by humans.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>H400 oral epithelial cell line was pre\u2010conditioned with curcumin and the production of cytokines was measured by enzyme\u2010linked immunosorbent assay (ELISA) and translocation of transcription factors was used to monitor inflammatory responses. Haem oxygenase (HO\u20101) expression and molecules that HO\u20101 releases were evaluated for their potential to reduce the quantity of cytokine production. Immunofluorescence microscopy and Western blotting were used to evaluate changes in transcription factor and enzyme location.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Pre\u2010conditioning of H400 cells with a sub\u2010apoptotic concentration of curcumin (20\u2009\u03bcM) attenuated secretion of Granulocyte\u2010Macrophage \u2013 Colony\u2010Stimulating Factor (GM\u2010CSF) and reduced NFkB nuclear translocation. This pre\u2010conditioning caused an increase in nuclear Nrf2; an initial drop (at 8\u00a0h) followed by an adaptive increase (at 24\u2009h) in glutathione; and an increase in haem oxygenase (HO\u20101) expression. Inhibition of HO\u20101 by SnPPIX prevented the curcumin\u2010induced attenuation of GM\u2010CSF production. HO\u20101 catalyses the breakdown of haem to carbon monoxide, free iron and biliverdin: the HO\u20101\/CO anti\u2010inflammatory pathway. Elevations in carbon monoxide, achieved using carbon monoxide releasing molecule\u20102 (CORM2) treatment alone abrogated <jats:italic>F. nucleatum<\/jats:italic>\u2010induced cytokine production. Biliverdin is converted to bilirubin by biliverdin reductase (BVR). This pleiotropic protein was found to increase in cell membrane expression upon curcumin treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Curcumin decreased inflammatory cytokine production induced by <jats:italic>Fusobacterium nucleatum<\/jats:italic> in H400 oral epithelial cells. The mechanism of action appears to be driven by the increase of haem oxygenase and the production of carbon monoxide.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jre.13114","type":"journal-article","created":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T11:31:37Z","timestamp":1678879897000},"page":"634-645","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Pre\u2010conditioning of gingival epithelial cells with sub\u2010apoptotic concentrations of curcumin prevents pro\u2010inflammatory cytokine release"],"prefix":"10.1111","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1154-7266","authenticated-orcid":false,"given":"Melissa M.","family":"Grant","sequence":"first","affiliation":[{"name":"Periodontal Research Group, School of Dentistry, Institute of Clinical Sciences and National Institute of Health Research (NIHR) Birmingham Biomedical Research Centre University of Birmingham and Birmingham Dental Hospital  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann E.","family":"Scott","sequence":"additional","affiliation":[{"name":"Unilever Oral Care  Bebington, Wirral UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John B.","family":"Matthews","sequence":"additional","affiliation":[{"name":"Periodontal Research Group, School of Dentistry, Institute of Clinical Sciences and National Institute of Health Research (NIHR) Birmingham Biomedical Research Centre University of Birmingham and Birmingham Dental Hospital  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen R.","family":"Griffiths","sequence":"additional","affiliation":[{"name":"Swansea University  Swansea UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain L. 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