Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China.
Department of Dermatology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China.
ACS Infect Dis. 2023 Nov 10;9(11):2299-2305. doi: 10.1021/acsinfecdis.3c00348. Epub 2023 Oct 16.
Exosomes have been implicated in vascular damage in recent research. The influence of dendritic cell-derived exosomes generated by () on the inflammatory process of vascular cells was examined in this study. Human umbilical vein endothelial cells (HUVECs) were cocultured with exosomes isolated from dendritic cells induced by . Western blot and reverse transcription-quantitative real-time polymerase chain reaction were used to assess toll-like receptor 4 (TLR4) expression and the quantity of proinflammatory cytokines. The findings showed that the expression of TLR4 was considerably upregulated, and TLR4 knockdown dramatically reduced ), interleukin-6 (), and tumor necrosis factor- () production in exosome-treated HUVECs. Furthermore, TLR4 silencing reduced myeloid differentiation primary response protein 88 (MyD88) and (NF-κB) levels in exosome-treated HUVECs. Additionally, suppression of the activity of NF-κB with BAY11-7082, an NF-κB inhibitor, also reduced the exosome-treated inflammatory response. Our results suggested that dendritic cell-derived exosomes stimulated by induced endothelial cell inflammation, and the TLR4/MyD88/NF-κB signal axis was activated, significantly increasing , , and expression. This may have a significant role in the vascular inflammatory response in syphilis, which would contribute to the understanding of the pathogenesis of syphilis and the host immunological response to .
外泌体在最近的研究中被牵连到血管损伤中。本研究探讨了（）来源的树突状细胞衍生的外泌体对血管细胞炎症过程的影响。将人脐静脉内皮细胞（HUVEC）与 诱导的树突状细胞分离的外泌体共培养。使用 Western blot 和逆转录定量实时聚合酶链反应来评估 toll 样受体 4（TLR4）表达和促炎细胞因子的数量。结果表明，TLR4 的表达显著上调，并且 TLR4 敲低可显著减少外泌体处理的 HUVEC 中 TLR4 表达和促炎细胞因子白细胞介素-6 (IL-6) 和肿瘤坏死因子-α (TNF-α) 的产生。此外，TLR4 沉默降低了外泌体处理的 HUVEC 中的髓样分化初级反应蛋白 88 (MyD88) 和核因子-κB (NF-κB) 水平。此外，使用 NF-κB 抑制剂 BAY11-7082 抑制 NF-κB 的活性也降低了外泌体处理的炎症反应。我们的结果表明，（）刺激的树突状细胞衍生的外泌体诱导内皮细胞炎症，并且激活了 TLR4/MyD88/NF-κB 信号轴，显著增加了 IL-6、TNF-α 和 IL-1β 的表达。这可能在梅毒中的血管炎症反应中具有重要作用，有助于理解梅毒的发病机制和宿主对梅毒的免疫反应。
