患有皮肤瘙痒症的血液透析患者的金黄色葡萄球菌皮肤定植以及金黄色葡萄球菌分泌的α毒素对丝胶蛋白表达的影响。

Yen-Yu Tsai, Ying-Jung Chen, Long-Sen Chang, Cheng-Ching Wu
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摘要

金黄色葡萄球菌(S. aureus)通常寄居在长期护理机构居民的皮肤上,但其在血液透析(HD)患者皮肤上的定植和影响尚未得到研究。本研究的目的是调查金黄色葡萄球菌在瘙痒性和非瘙痒性血液透析患者皮肤上的定植情况,以及金黄色葡萄球菌和金黄色葡萄球菌分泌的α-毒素对皮肤屏障功能相关蛋白表达的影响。本研究通过实时聚合酶链反应发现,与非瘙痒性 HD 患者和健康受试者相比,瘙痒性 HD 患者的金黄色葡萄球菌相对计数更高。金黄色葡萄球菌和α-毒素降低了角朊细胞中芳基烃受体(AHR)、类卵转录抑制因子1(OVOL1)和丝胶蛋白(FLG)的mRNA和蛋白表达水平。此外,抗α溶血素(anti-hla)被用作α毒素中和剂,它成功地抑制了金黄色葡萄球菌诱导的AHR、OVOL1和FLG mRNA和蛋白表达下调。从机理上讲,α-毒素可通过阻止AHR招募到FLG启动子区域来降低FLG的活性。总之,瘙痒性HD患者的金黄色葡萄球菌定植率较高,金黄色葡萄球菌分泌的α-毒素通过AHR-FLG轴抑制FLG的表达。
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Skin colonization by Staphylococcus aureus in hemodialysis patients with pruritus and the effect of Staphylococcus aureus-secreted α-toxin on filaggrin expression.

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.

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