STD Institute, Shanghai Dermatology Hospital, Tongji University School of Medicine, Shanghai 200443, China.
Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China.
Biosci Rep. 2019 Aug 7;39(8). doi: 10.1042/BSR20190686. Print 2019 Aug 30.
Syphilis caused by () infection is accompanied by inflammatory injury of tissue, and has a worldwide distribution and increasing incidence over the past decade. Tp17 has been reported to be a strong membrane immunogen, and was initially observed to play a role in inflammation during syphilis, reacting intensely with human syphilitic sera. We therefore used recombinant Tp17 (rTp17) as a stimulator in our study. Increasing evidence has demonstrated that microRNA (miRNA)-containing exosomes have emerged as a potential effective therapeutic target for many diseases. However, the biological functions and molecular mechanisms of miR-216a-5p in syphilis pathogenesis remain unknown. Our study first identified dramatically decreased miR-216a-5p in plasma of syphilis patients compared with the healthy control, which was negatively correlated with the expression of inflammatory cytokines, including IL-1β, IL-6, and TNF-α. Moreover, endothelial cells treated with miR-216a-5p-containing exosomes significantly attenuated the rTp17-induced inflammatory response. More importantly, we identified that miR-216a-5p could bind to the 3'-untranslated region (UTR) of Toll-like receptor (TLR) 4 (TLR4), and overexpression of TLR4 largely rescued the miR-216a-5p-mediated suppression of rTp17-induced inflammatory cytokine production and the TLR4-MYD88 signaling pathway. Thus, our results reveal a novel role of miR-216a-5p-containing exosomes in endothelial cells, implying a potential therapeutic target for inflammation in syphilis patients.
由 （）感染引起的梅毒伴随着组织的炎症损伤，具有全球分布，且在过去十年中的发病率不断增加。Tp17 已被报道为一种强烈的膜免疫原，最初观察到它在梅毒炎症反应中发挥作用，与人类梅毒血清强烈反应。因此，我们在研究中使用重组 Tp17（rTp17）作为刺激物。越来越多的证据表明，含有 microRNA（miRNA）的外泌体已成为许多疾病潜在有效的治疗靶点。然而，miR-216a-5p 在梅毒发病机制中的生物学功能和分子机制仍不清楚。我们的研究首次发现梅毒患者血浆中的 miR-216a-5p 明显降低，与炎症细胞因子（包括 IL-1β、IL-6 和 TNF-α）的表达呈负相关。此外，用含有 miR-216a-5p 的外泌体处理的内皮细胞显著减弱了 rTp17 诱导的炎症反应。更重要的是，我们发现 miR-216a-5p 可以与 Toll 样受体（TLR）4 的 3'非翻译区（UTR）结合，TLR4 的过表达在很大程度上挽救了 miR-216a-5p 介导的 rTp17 诱导的炎症细胞因子产生和 TLR4-MYD88 信号通路的抑制作用。因此，我们的结果揭示了 miR-216a-5p 在外皮细胞中的新作用，暗示了梅毒患者炎症的潜在治疗靶点。
