Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, Kaohsiung, Taiwan.
J Dermatol. 2024 Oct;51(10):1318-1328. doi: 10.1111/1346-8138.17326. Epub 2024 Jun 18.
Staphylococcus aureus (S. aureus) commonly reside on human skin in residents in long-term care facilities, yet its colonization and impact on the skin of hemodialysis (HD) patients have yet to be studied. The aim of the present study was to investigate the colonization of S. aureus on the skin of pruritic and non-pruritic HD patients, and the influence of S. aureus and S. aureus-secreted α-toxin on skin barrier function-related protein expression. In this study, a higher relative S. aureus count in pruritic HD patients compared to non-pruritic HD patients and healthy subjects were revealed by real-time polymerase chain reaction. S. aureus and α-toxin decreased mRNA and protein expression levels of aryl hydrocarbon receptor (AHR), ovo-like transcriptional repressor 1 (OVOL1), and filaggrin (FLG) in keratinocytes. In addition, anti-alpha-hemolysin (anti-hla) was used as an α-toxin neutralizer, and it successfully abrogated S. aureus-induced AHR, OVOL1, and FLG mRNA and protein expression downregulation. Mechanistically, α-toxin could decrease FLG activity by preventing the recruitment of AHR to the FLG promoter region. In conclusion, pruritic HD patients had higher S. aureus colonization, with S. aureus-secreted α-toxin suppressing FLG expression through the AHR-FLG axis.
金黄色葡萄球菌（S. aureus）通常存在于长期护理机构居民的人类皮肤上，但它在血液透析（HD）患者皮肤上的定植及其影响尚未得到研究。本研究旨在调查瘙痒和非瘙痒性 HD 患者皮肤金黄色葡萄球菌定植情况，以及金黄色葡萄球菌及其分泌的α-毒素对皮肤屏障功能相关蛋白表达的影响。在本研究中，实时聚合酶链反应显示瘙痒性 HD 患者皮肤的金黄色葡萄球菌相对计数高于非瘙痒性 HD 患者和健康受试者。金黄色葡萄球菌和α-毒素降低了角质形成细胞中芳香烃受体（AHR）、卵黄样转录阻遏物 1（OVOL1）和丝聚合蛋白（FLG）的 mRNA 和蛋白表达水平。此外，抗α-溶血素（抗 hla）被用作α-毒素中和剂，成功阻断了金黄色葡萄球菌诱导的 AHR、OVOL1 和 FLG mRNA 和蛋白表达下调。从机制上讲，α-毒素通过阻止 AHR 募集到 FLG 启动子区域来降低 FLG 活性。总之，瘙痒性 HD 患者金黄色葡萄球菌定植较高，金黄色葡萄球菌分泌的α-毒素通过 AHR-FLG 轴抑制 FLG 表达。
