Treponema pallidum Induces the Secretion of HDVSMC Inflammatory Cytokines to Promote the Migration and Adhesion of THP-1 Cells
Treponema pallidum Induces the Secretion of HDVSMC Inflammatory Cytokines to Promote the Migration and Adhesion of THP-1 Cells
复制标题
梅毒螺旋体诱导HDVSMC炎症细胞因子分泌促进THP-1细胞迁移和粘附
DOI：
10.3389/fcimb.2019.00220
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发表时间：
2019-06-21
影响因子：
5.7
通讯作者：
Yang, Tian-Ci
中科院分区：
文献类型：
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作者：
Gao, Zheng-Xiang;Liu, Li-Li;Yang, Tian-Ci
梅毒是由梅毒螺旋体（Treponema pallidum，T.苍白球），其特征在于血管累及动脉内膜炎和动脉周围炎。在梅毒的免疫发病机制中，小动脉中浸润的免疫细胞与人真皮血管平滑肌细胞（HDVSMCs）的相互作用知之甚少。在本研究中，我们证明了用T.苍白球可上调白细胞介素（IL）-6、单核细胞趋化蛋白-1（MCP-1）和细胞间粘附分子-1（ICAM-1）的基因转录和蛋白表达，且呈剂量和时间依赖性。此外，抗MCP-1和抗ICAM-1中和抗体分别显著抑制THP-1细胞与HDVSMC的迁移和粘附。进一步的研究表明T.苍白球激活HDVSMCs的NF-κ B信号通路。抑制NF-κ B可抑制T.苍白球诱导的IL-6、MCP-1和ICAM-1表达。此外，THP-1细胞在T.用NF-κ B抑制剂预处理可显著降低苍白球处理的HDVSMC。这些结果表明T.苍白球通过NF-κ B B信号通路诱导HDVSMCs产生IL-6、MCP-1和ICAM-1，促进THP-1细胞与HDVSMCs的粘附和迁移，这可能为T.苍白球感染
The pathological features of syphilis, a disease caused by Treponema pallidum (T. pallidum), are characterized by vascular involvement with endarteritis and periarteritis. Little is known about the interactions of infiltrating immunocytes with human dermal vascular smooth muscle cells (HDVSMCs) in arterioles during the immunopathogenesis of syphilis. In the present study, we demonstrated that stimulation of HDVSMCs with T. pallidum resulted in the upregulated gene transcription and protein expression of interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1) in a dose- and time-dependent manner. Moreover, 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 T. pallidum activated the NF-kappa B signaling pathway in HDVSMCs. Inhibition of NF-kappa B suppressed T. pallidum-induced IL-6, MCP-1, and ICAM-1 expression. In addition, the migration and adhesion of THP-1 cells to T. pallidum-treated HDVSMCs were significantly decreased by pretreatment with an NF-kappa B inhibitor. These findings demonstrate that T. pallidum induces the production of IL-6, MCP-1, and ICAM-1 in HDVSMCs and promotes the adherence and migration of THP-1 cells to HDVSMCs through the NF-kappa B signaling pathway, which may provide new insight into the pathogenesis of T. pallidum infection.