Candida albicans induces TLR2/MyD88/NF-κB signaling and inflammation in oral lichen planus-derived keratinocytes
Introduction: The risk of oral lichen planus (OLP), a chronic inflammatory oral mucosal disease, becoming malignant increases by 21-fold in patients with fungal infection. This study examined the impact of Candida albicans exposure on Toll-like receptor (TLR) signaling in primary keratinocyte cultu...
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The Journal of Infection in Developing Countries
2018-09-01
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| Series: | Journal of Infection in Developing Countries |
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| Online Access: | https://jidc.org/index.php/journal/article/view/8062 |
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| author | Jianwei Liu Fanghui Geng Hongying Sun Xiaxia Wang Hui Zhang Qiaozhen Yang Jie Zhang |
| author_facet | Jianwei Liu Fanghui Geng Hongying Sun Xiaxia Wang Hui Zhang Qiaozhen Yang Jie Zhang |
| author_sort | Jianwei Liu |
| collection | DOAJ |
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Introduction: The risk of oral lichen planus (OLP), a chronic inflammatory oral mucosal disease, becoming malignant increases by 21-fold in patients with fungal infection. This study examined the impact of Candida albicans exposure on Toll-like receptor (TLR) signaling in primary keratinocyte cultures obtained from OLP patients.
Methodology: Following co-culture of primary OLP keratinocyte cultures with C. albicans for 24 hours, inflammatory cytokine concentrations were determined by ELISA. TLR2, MyD88, and NF-κBp65 mRNA and protein expression were assessed using quantitative RT-PCR and Western blot analyses, respectively. Keratinocyte apoptosis was also determined by flow cytometry.
Results: IL-10, IL-8, IL-2, and TNF-ɑ levels were significantly higher following co-culture with C. albicans (all p ≤ 0.034). MyD88, NF-κB p65, and TLR2 mRNA (all p < 0.001) and protein (all p ≤ 0.004) expression levels were significantly higher in OLP keratinocytes following C. albicans exposure. Finally, the apoptosis rates of OLP keratinocytes were 21.2%, 29.4%, and 25.4% for the control cells and 3.9%, 5.6%, and 4.4% for those exposed to C. albicans, suggesting that co-culture with C. albicans inhibits the apoptosis of OLP keratinocytes.
Conclusions: C. albicans activates the TLR2/MyD88/NF-κB signaling pathway in OLP keratinocytes, resulting in increased cytokine expression and decreased keratinocyte apoptosis. Two key events in the pathogenesis of OLP and its progression to malignancy, namely increased inflammation and decreased apoptosis, were induced by exposure to C. albicans. Thus, targeting this signaling pathway may represent a novel therapeutic strategy to prevent OLP malignant transformation.
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| format | Article |
| id | doaj-art-e6221b7f62904f45bdad372dbbce0b02 |
| institution | OA Journals |
| issn | 1972-2680 |
| language | English |
| publishDate | 2018-09-01 |
| publisher | The Journal of Infection in Developing Countries |
| record_format | Article |
| series | Journal of Infection in Developing Countries |
| spelling | doaj-art-e6221b7f62904f45bdad372dbbce0b022025-08-20T02:16:06ZengThe Journal of Infection in Developing CountriesJournal of Infection in Developing Countries1972-26802018-09-01120910.3855/jidc.8062Candida albicans induces TLR2/MyD88/NF-κB signaling and inflammation in oral lichen planus-derived keratinocytesJianwei Liu0Fanghui Geng1Hongying Sun2Xiaxia Wang3Hui Zhang4Qiaozhen Yang5Jie Zhang6Shandong University Affilicated Qilu Hospital, Jinan, Shandong, ChinaHuashan Hospital, Fudan University, Shanghai, ChinaHuashan Hospital, Fudan University, Shanghai, ChinaHuashan Hospital, Fudan University, Shanghai, ChinaHuashan Hospital, Fudan UniversityHuashan Hospital, Fudan University, Shanghai, ChinaHuashan Hospital, Fudan University, Shanghai, China Introduction: The risk of oral lichen planus (OLP), a chronic inflammatory oral mucosal disease, becoming malignant increases by 21-fold in patients with fungal infection. This study examined the impact of Candida albicans exposure on Toll-like receptor (TLR) signaling in primary keratinocyte cultures obtained from OLP patients. Methodology: Following co-culture of primary OLP keratinocyte cultures with C. albicans for 24 hours, inflammatory cytokine concentrations were determined by ELISA. TLR2, MyD88, and NF-κBp65 mRNA and protein expression were assessed using quantitative RT-PCR and Western blot analyses, respectively. Keratinocyte apoptosis was also determined by flow cytometry. Results: IL-10, IL-8, IL-2, and TNF-ɑ levels were significantly higher following co-culture with C. albicans (all p ≤ 0.034). MyD88, NF-κB p65, and TLR2 mRNA (all p < 0.001) and protein (all p ≤ 0.004) expression levels were significantly higher in OLP keratinocytes following C. albicans exposure. Finally, the apoptosis rates of OLP keratinocytes were 21.2%, 29.4%, and 25.4% for the control cells and 3.9%, 5.6%, and 4.4% for those exposed to C. albicans, suggesting that co-culture with C. albicans inhibits the apoptosis of OLP keratinocytes. Conclusions: C. albicans activates the TLR2/MyD88/NF-κB signaling pathway in OLP keratinocytes, resulting in increased cytokine expression and decreased keratinocyte apoptosis. Two key events in the pathogenesis of OLP and its progression to malignancy, namely increased inflammation and decreased apoptosis, were induced by exposure to C. albicans. Thus, targeting this signaling pathway may represent a novel therapeutic strategy to prevent OLP malignant transformation. https://jidc.org/index.php/journal/article/view/8062ApoptosisCandida albicanskeratinocyteoral lichen planusToll-like receptor |
| spellingShingle | Jianwei Liu Fanghui Geng Hongying Sun Xiaxia Wang Hui Zhang Qiaozhen Yang Jie Zhang Candida albicans induces TLR2/MyD88/NF-κB signaling and inflammation in oral lichen planus-derived keratinocytes Journal of Infection in Developing Countries Apoptosis Candida albicans keratinocyte oral lichen planus Toll-like receptor |
| title | Candida albicans induces TLR2/MyD88/NF-κB signaling and inflammation in oral lichen planus-derived keratinocytes |
| title_full | Candida albicans induces TLR2/MyD88/NF-κB signaling and inflammation in oral lichen planus-derived keratinocytes |
| title_fullStr | Candida albicans induces TLR2/MyD88/NF-κB signaling and inflammation in oral lichen planus-derived keratinocytes |
| title_full_unstemmed | Candida albicans induces TLR2/MyD88/NF-κB signaling and inflammation in oral lichen planus-derived keratinocytes |
| title_short | Candida albicans induces TLR2/MyD88/NF-κB signaling and inflammation in oral lichen planus-derived keratinocytes |
| title_sort | candida albicans induces tlr2 myd88 nf κb signaling and inflammation in oral lichen planus derived keratinocytes |
| topic | Apoptosis Candida albicans keratinocyte oral lichen planus Toll-like receptor |
| url | https://jidc.org/index.php/journal/article/view/8062 |
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