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Bacteria, such as Porphyromonas gingivalis and Fusobacterium nucleatum, play a pivotal role in periodontitis development because they contribute to dysbiosis and tissue destruction. Thus, comprehending the interplay between these bacteria and their impacts on inflammation holds significant relevance in clinical understanding and treatment advancement. In the present work, we explored, for the first time, their impacts on the expressions of pro-inflammatory mediators after infecting oral keratinocytes (OKs) with a co-culture of pre-incubated P. gingivalis and F. nucleatum. Our results show that the co-culture increases IL-1\u03b2, IL-8, and TNF-\u03b1 expressions, synergistically augments IL-6, and translocates NF-kB to the cell nucleus. These changes in pro-inflammatory mediators\u2014associated with chronic inflammation and cancer\u2014correlate with an increase in cell migration following infection with the co-cultured bacteria or P. gingivalis alone. This effect depends on TLR4 because TLR4 knockdown notably impacts IL-6 expression and cell migration. Our study unveils, for the first time, crucial insights into the outcomes of their co-culture on virulence, unraveling the role of bacterial interactions in polymicrobial diseases and potential links to oral cancer.<\/jats:p>","DOI":"10.3390\/ijms25073611","type":"journal-article","created":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T12:47:11Z","timestamp":1711370831000},"page":"3611","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Co-Culture of P. gingivalis and F. nucleatum Synergistically Elevates IL-6 Expression via TLR4 Signaling in Oral Keratinocytes"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-8540-940X","authenticated-orcid":false,"given":"Lucas","family":"Y\u00e1\u00f1ez","sequence":"first","affiliation":[{"name":"Microbial Interactions Laboratory, Faculty of Dentistry, Universidad Andr\u00e9s Bello, Santiago 8370133, Chile"},{"name":"Advanced Center for Chronic Diseases (ACCDiS), Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8286-5512","authenticated-orcid":false,"given":"Cristopher","family":"Soto","sequence":"additional","affiliation":[{"name":"Microbial Interactions Laboratory, Faculty of Dentistry, Universidad Andr\u00e9s Bello, Santiago 8370133, Chile"},{"name":"Advanced Center for Chronic Diseases (ACCDiS), Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9ctor","family":"Tapia","sequence":"additional","affiliation":[{"name":"Microbial Interactions Laboratory, Faculty of Dentistry, Universidad Andr\u00e9s Bello, Santiago 8370133, Chile"},{"name":"Advanced Center for Chronic Diseases (ACCDiS), Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mart\u00edn","family":"Pacheco","sequence":"additional","affiliation":[{"name":"Microbial Interactions Laboratory, Faculty of Dentistry, Universidad Andr\u00e9s Bello, Santiago 8370133, Chile"},{"name":"Advanced Center for Chronic Diseases (ACCDiS), Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javiera","family":"Tapia","sequence":"additional","affiliation":[{"name":"Microbial Interactions Laboratory, Faculty of Dentistry, Universidad Andr\u00e9s Bello, Santiago 8370133, Chile"},{"name":"Advanced Center for Chronic Diseases (ACCDiS), Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Osses","sequence":"additional","affiliation":[{"name":"Microbial Interactions Laboratory, Faculty of Dentistry, Universidad Andr\u00e9s Bello, Santiago 8370133, Chile"},{"name":"Advanced Center for Chronic Diseases (ACCDiS), Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Salinas","sequence":"additional","affiliation":[{"name":"Oral Microbiology and Immunology Laboratory, Department of Pathology and Oral Medicine, Faculty of Dentistry, Universidad de Chile, Santiago 8380492, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Rojas-Celis","sequence":"additional","affiliation":[{"name":"Virology Laboratory, Department of Biology, Faculty of Sciences, Universidad de Chile, Santiago 7800003, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1617-6401","authenticated-orcid":false,"given":"Anilei","family":"Hoare","sequence":"additional","affiliation":[{"name":"Oral Microbiology and Immunology Laboratory, Department of Pathology and Oral Medicine, Faculty of Dentistry, Universidad de Chile, Santiago 8380492, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew F. G.","family":"Quest","sequence":"additional","affiliation":[{"name":"Advanced Center for Chronic Diseases (ACCDiS), Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile"},{"name":"Cellular Communication Laboratory, Center for Studies on Exercise, Metabolism and Cancer (CEMC), Program of Cell and Molecular Biology, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"D\u00edaz-Elizondo","sequence":"additional","affiliation":[{"name":"Microbial Interactions Laboratory, Faculty of Dentistry, Universidad Andr\u00e9s Bello, Santiago 8370133, Chile"},{"name":"Advanced Center for Chronic Diseases (ACCDiS), Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9506-1716","authenticated-orcid":false,"given":"Jos\u00e9 Manuel","family":"P\u00e9rez-Donoso","sequence":"additional","affiliation":[{"name":"BioNanotechnology and Microbiology Laboratory, Center for Bioinformatics and Integrative Biology (CBIB), Faculty of Life Sciences, Universidad Andr\u00e9s Bello, Santiago 8370186, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denisse","family":"Bravo","sequence":"additional","affiliation":[{"name":"Microbial Interactions Laboratory, Faculty of Dentistry, Universidad Andr\u00e9s Bello, Santiago 8370133, Chile"},{"name":"Advanced Center for Chronic Diseases (ACCDiS), Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1111\/prd.12453","article-title":"Influence of epigenetics on periodontitis and peri-implantitis pathogenesis","volume":"90","author":"Larsson","year":"2022","journal-title":"Periodontol. 2000"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1111\/prd.12200","article-title":"Periodontitis epidemiology: Is periodontitis under-recognized, over-diagnosed, or both?","volume":"75","author":"Papapanou","year":"2017","journal-title":"Periodontol. 2000"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1038\/ismej.2012.174","article-title":"The subgingival microbiome in health and periodontitis and its relationship with community biomass and inflammation","volume":"7","author":"Abusleme","year":"2013","journal-title":"ISME J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1002\/ijc.31937","article-title":"Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods","volume":"144","author":"Ferlay","year":"2019","journal-title":"Int. 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