Center of Clinical Laboratory, Zhongshan Hospital, School of Medicine, Xiamen University, Xiamen, 361004, China; Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, 361004, China.
Center of Clinical Laboratory, Zhongshan Hospital, School of Medicine, Xiamen University, Xiamen, 361004, China.
Exp Cell Res. 2019 Aug 1;381(1):150-162. doi: 10.1016/j.yexcr.2019.04.035. Epub 2019 May 7.
Vascular inflammation is a complex and multifactorial pathophysiological process that plays a crucial role in all stages of syphilis and is responsible for tissue damage. Little is known about the interactions of infiltrating immunocytes with human dermal vascular smooth muscle cells (HDVSMCs) in arterioles during the immunopathogenesis of syphilis. The Treponema pallidum subsp. pallidum membrane protein Tp47 is considered a major inducer of inflammation initiation and development. In this study, we demonstrated that Tp47 promoted the migration and adhesion of THP-1 cells to HDVSMCs. Furthermore, Tp47 increased monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule-1 (ICAM-1) mRNA and protein expression levels in a dose- and time-dependent manner. The migration and adhesion of THP-1 cells to HDVSMCs were significantly suppressed by anti-MCP-1 and anti-ICAM-1 neutralizing antibodies, respectively. Further studies revealed that treatment of HDVSMCs with Tp47 activated the PI3K/Akt, p38 MAPK and NF-κB signalling pathways. Inhibition of PI3K/Akt, p38 MAPK and NF-κB suppressed the MCP-1 and ICAM-1 expression induced by Tp47. In addition, the migration and adhesion of THP-1 cells to Tp47-treated HDVSMCs were significantly decreased by pretreatment with PI3K/Akt, p38 MAPK and NF-κB inhibitors. These findings demonstrate that Tp47 promotes the migration and adherence of THP-1 cells to HDVSMCs by inducing MCP-1 and ICAM-1 expression, which is mediated by activation of the PI3K/Akt, p38 MAPK and NF-κB pathways. This study provides a novel potential therapeutic strategy for controlling the vascular inflammatory response in syphilis patients.
血管炎症是一个复杂的多因素病理生理过程，在梅毒的所有阶段都起着至关重要的作用，是组织损伤的原因。在梅毒的免疫发病机制中，关于浸润免疫细胞与人类真皮血管平滑肌细胞（HDVSMCs）在小动脉中的相互作用知之甚少。苍白密螺旋体亚种苍白密螺旋体膜蛋白 Tp47 被认为是炎症启动和发展的主要诱导剂。在这项研究中，我们证明了 Tp47 促进了 THP-1 细胞向 HDVSMCs 的迁移和黏附。此外，Tp47 以剂量和时间依赖的方式增加单核细胞趋化蛋白-1（MCP-1）和细胞间黏附分子-1（ICAM-1）mRNA 和蛋白表达水平。抗 MCP-1 和抗 ICAM-1 中和抗体分别显著抑制 THP-1 细胞向 HDVSMCs 的迁移和黏附。进一步的研究表明，Tp47 处理 HDVSMCs 激活了 PI3K/Akt、p38 MAPK 和 NF-κB 信号通路。PI3K/Akt、p38 MAPK 和 NF-κB 的抑制抑制了 Tp47 诱导的 MCP-1 和 ICAM-1 表达。此外，PI3K/Akt、p38 MAPK 和 NF-κB 抑制剂预处理显著降低了 THP-1 细胞向 Tp47 处理的 HDVSMCs 的迁移和黏附。这些发现表明，Tp47 通过诱导 MCP-1 和 ICAM-1 表达促进 THP-1 细胞向 HDVSMCs 的迁移和黏附，这是通过激活 PI3K/Akt、p38 MAPK 和 NF-κB 途径介导的。这项研究为控制梅毒患者的血管炎症反应提供了一种新的潜在治疗策略。
