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In contrast to other members of the genus <jats:italic>Corynebacterium<\/jats:italic>, such as toxigenic <jats:italic>Corynebacterium diphtheriae<\/jats:italic> or the opportunistic pathogen <jats:italic>Corynebacterium jeikeium<\/jats:italic>, several studies suggest that <jats:italic>C. t<\/jats:italic>. may play a role in skin health and disease. However, the mechanisms underlying these effects remain poorly understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To investigate whether <jats:italic>C. t<\/jats:italic>. induces inflammatory pathways in primary human epidermal keratinocytes (HEKs) and human cutaneous squamous carcinoma cells (SCCs), cell culture, reverse transcription\u2010polymerase chain reaction (PCR), enzyme\u2010linked immunosorbent assay, immunofluorescence microscopy, Western blot, chromatin immunoprecipitation\u2010PCR, small interfering RNA knockdown and luciferase reporter expression system were used.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Herein, we demonstrate that <jats:italic>C. t<\/jats:italic>. upregulates the messenger RNA (mRNA) and protein levels of inflammatory mediators in two human skin cell lines, HEKs and SCCs. We further show activation of the canonical nuclear factor\u2010\u03baB (NF\u2010\u03baB) pathway in response to <jats:italic>C. t<\/jats:italic>. infection, including phosphorylation of the inhibitor of \u03baB (I\u03baB), the nuclear translocation of NF\u2010\u03baB subunit (NF\u2010\u03baB\u2010P<jats:sub>65<\/jats:sub>) and the recruitment of NF\u2010\u03baB\u2010P<jats:sub>65<\/jats:sub> and RNA polymerase to the NF\u2010\u03baB response elements at the promoter region of the inflammatory genes. Lastly, the data confirm that <jats:italic>C. t<\/jats:italic>.\u2010induced tumor necrosis factor mRNA expression in HEKs is toll\u2010like receptor 2 (TLR<jats:sub>2<\/jats:sub>) dependent.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results offer a mechanistic model for <jats:italic>C. t<\/jats:italic>.\u2010induced inflammation in human keratinocytes via TLR<jats:sub>2<\/jats:sub> and activation of I\u03baB kinase and downstream signaling through the canonical NF\u2010\u03baB pathway. Relevance to chronic inflammatory diseases of the skin and cutaneous oncology is discussed.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.284","type":"journal-article","created":{"date-parts":[[2020,1,8]],"date-time":"2020-01-08T05:30:03Z","timestamp":1578461403000},"page":"62-79","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["<i>Corynebacterium tuberculostearicum<\/i>, a human skin colonizer, induces the canonical nuclear factor\u2010\u03baB inflammatory signaling pathway in human skin cells"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9086-5934","authenticated-orcid":false,"given":"Mohammed O.","family":"Altonsy","sequence":"first","affiliation":[{"name":"Division of Dermatology, Department of Medicine University of Calgary  Calgary Canada"},{"name":"Department of Zoology, Faculty of Science Sohag University  Sohag 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