Corynebacterium tuberculostearicum, a human skin colonizer, induces the canonical nuclear factor‐κB inflammatory signaling pathway in human skin cells
| Autor: | Matthias Amrein, Paule Régine Mydlarski, Mohammed O. Altonsy, Gilles J. Lauzon, Wagdi Almishri, Habib A Kurwa, Anthony N. Gerber |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
keratinocytes lcsh:Immunologic diseases. Allergy Small interfering RNA Immunology IκB kinase Corynebacterium Transfection cutaneous squamous carcinoma cells Cell Line 03 medical and health sciences 0302 clinical medicine Corynebacterium jeikeium Humans Immunology and Allergy RNA Messenger Phosphorylation RNA Small Interfering Corynebacterium tuberculostearicum Original Research Gene knockdown Corynebacterium Infections biology Tumor Necrosis Factor-alpha IKK NF‐κB NF-kappa B biology.organism_classification Molecular biology I-kappa B Kinase Squamous carcinoma TLR2 030104 developmental biology inflammation Carcinoma Squamous Cell Signal transduction lcsh:RC581-607 Signal Transduction 030215 immunology |
| Zdroj: | Immunity, Inflammation and Disease, Vol 8, Iss 1, Pp 62-79 (2020) Immunity, Inflammation and Disease |
| ISSN: | 2050-4527 |
| Popis: | Introduction Corynebacterium tuberculostearicum (C. t.) is a ubiquitous bacterium that colonizes human skin. In contrast to other members of the genus Corynebacterium, such as toxigenic Corynebacterium diphtheriae or the opportunistic pathogen Corynebacterium jeikeium, several studies suggest that C. t. may play a role in skin health and disease. However, the mechanisms underlying these effects remain poorly understood. Methods To investigate whether C. t. induces inflammatory pathways in primary human epidermal keratinocytes (HEKs) and human cutaneous squamous carcinoma cells (SCCs), cell culture, reverse transcription‐polymerase chain reaction (PCR), enzyme‐linked immunosorbent assay, immunofluorescence microscopy, Western blot, chromatin immunoprecipitation‐PCR, small interfering RNA knockdown and luciferase reporter expression system were used. Results Herein, we demonstrate that C. t. 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‐κB (NF‐κB) pathway in response to C. t. infection, including phosphorylation of the inhibitor of κB (IκB), the nuclear translocation of NF‐κB subunit (NF‐κB‐P65) and the recruitment of NF‐κB‐P65 and RNA polymerase to the NF‐κB response elements at the promoter region of the inflammatory genes. Lastly, the data confirm that C. t.‐induced tumor necrosis factor mRNA expression in HEKs is toll‐like receptor 2 (TLR2) dependent. Conclusion Our results offer a mechanistic model for C. t.‐induced inflammation in human keratinocytes via TLR2 and activation of IκB kinase and downstream signaling through the canonical NF‐κB pathway. Relevance to chronic inflammatory diseases of the skin and cutaneous oncology is discussed. Corynebacterium tuberculostearicum (C. t.) may play a role in skin health and disease. C. t. upregulates the messenger RNA (mRNA) and protein levels of inflammatory mediators in the human skin cell via the activation of the canonical nuclear factor‐κB pathway. |
| Databáze: | OpenAIRE |
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