Muangsanit Papon, Tansirichaiya Supathep, Lapthanasupkul Puangwan, Leethanakul Chidchanok, Pimolbutr Kununya, Singhatanadgit Weerachai
Cell Technology and Tissue Engineering Research Team, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani, Thailand.
Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Odontology. 2025 May 21. doi: 10.1007/s10266-025-01119-z.
Oral lichen planus (OLP), a prevalent immune-mediated inflammatory condition, requires effective therapies. Topical corticosteroids, such as dexamethasone, are widely used for OLP treatment. However, they can predispose patients to secondary candidiasis, necessitating adjunctive therapy with antifungal agents like miconazole. Little is known about the cellular dynamics and toxicity of the combined use of dexamethasone and miconazole. This study examined the effect of dexamethasone on the antifungal activity of miconazole against Candida albicans and the effect of miconazole on the immunosuppressive activity of dexamethasone on human T cells. The cytotoxicity of dexamethasone alone and dexamethasone combined with miconazole on human oral keratinocytes and gingival fibroblasts was also determined using both in vitro monolayer and Transwell co-culture models. A 5-min incubation thrice daily cell treatment protocol was employed for all assays. Dexamethasone did not affect miconazole's antifungal efficacy, and a single exposure of miconazole inhibited over 99% of C. albicans growth. In monolayer cultures, 0.05% dexamethasone was non-toxic to keratinocytes and fibroblasts, while miconazole exhibited dose-dependent cytotoxicity at high concentrations. Transwell co-culture models confirmed this dose-dependent cytotoxicity, with higher miconazole concentrations causing increased apoptosis. Dexamethasone significantly reduced T cell viability, activation, and proliferation, unaffected by miconazole co-treatment. In conclusion, when used in combination at optimal concentrations, miconazole's antifungal activity and dexamethasone's anti-T-cell proliferation activity are retained without cytotoxicity to human oral cells. Further research is needed to validate these findings and develop evidence-based treatments for oral lichen planus.
口腔扁平苔藓(OLP)是一种常见的免疫介导性炎症疾病,需要有效的治疗方法。局部用皮质类固醇,如地塞米松,被广泛用于OLP的治疗。然而,它们会使患者易患继发性念珠菌病,因此需要与咪康唑等抗真菌药物联合治疗。关于地塞米松和咪康唑联合使用的细胞动力学和毒性知之甚少。本研究考察了地塞米松对咪康唑抗白色念珠菌活性的影响,以及咪康唑对地塞米松对人T细胞免疫抑制活性的影响。还使用体外单层培养和Transwell共培养模型测定了单独使用地塞米松以及地塞米松与咪康唑联合使用对人口腔角质形成细胞和牙龈成纤维细胞的细胞毒性。所有测定均采用每日三次、每次5分钟的细胞孵育处理方案。地塞米松不影响咪康唑的抗真菌疗效,单次暴露的咪康唑可抑制超过99%的白色念珠菌生长。在单层培养中,0.05%的地塞米松对角质形成细胞和成纤维细胞无毒,而咪康唑在高浓度时表现出剂量依赖性细胞毒性。Transwell共培养模型证实了这种剂量依赖性细胞毒性,咪康唑浓度越高,细胞凋亡增加。地塞米松显著降低T细胞活力、活化和增殖,联合使用咪康唑不影响其作用。总之,在最佳浓度联合使用时,咪康唑的抗真菌活性和地塞米松的抗T细胞增殖活性得以保留,且对人口腔细胞无细胞毒性。需要进一步研究来验证这些发现,并为口腔扁平苔藓开发循证治疗方法。