Center of Clinical Laboratory, Zhongshan Hospital, School of Medicine, Xiamen University, Xiamen, China; Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, China.
Center of Clinical Laboratory, Zhongshan Hospital, School of Medicine, Xiamen University, Xiamen, China.
Int Immunopharmacol. 2019 Oct;75:105744. doi: 10.1016/j.intimp.2019.105744. Epub 2019 Jul 15.
Although the infiltration of monocytes into local lesions is an obvious pathological manifestation in the pathogenesis of syphilis, little is known about the role of metalloproteinase (MMP)/tissue inhibitor of metalloproteinases (TIMP) imbalance in the migration/invasion of THP-1 cells induced by Treponema pallidum (T. pallidum). The influence of T. pallidum on the invasion and migration of THP-1 cells was evaluated. Changes in the MMP/TIMP balance and the mechanisms underlying the involvement of the MAPK and NF-κB signaling pathways in this process were explored. T. pallidum induced the migration/invasion of THP-1 cells and the mRNA and protein expression of MMP-1, MMP-9 and TIMP-1. The mRNA expression of TIMP-2 was reduced, and the protein expression of TIMP-2 was not changed. The MMP-1/TIMP-1, MMP-1/TIMP-2, MMP-9/TIMP-1 and MMP-9/TIMP-2 ratios were increased. Inhibition of JNK, MEK/ERK, p38 MAPK and NF-κB significantly decreased the MMP/TIMP ratio and ultimately suppressed the migration/invasion of THP-1 cells. These findings revealed that MMP/TIMP imbalances induced by T. pallidum enhanced THP-1 cell migration and invasion via MAPK and NF-κB signaling pathway activation, which revealed a novel step in syphilis pathophysiology.
虽然单核细胞浸润局部病变是梅毒发病机制中的一个明显的病理学表现，但关于梅毒螺旋体（T. pallidum）诱导的 THP-1 细胞迁移/侵袭中金属蛋白酶（MMP）/金属蛋白酶抑制剂（TIMP）失衡的作用知之甚少。评估了 T. pallidum 对 THP-1 细胞侵袭和迁移的影响。探讨了 MAPK 和 NF-κB 信号通路参与这一过程中 MMP/TIMP 平衡的变化及其机制。T. pallidum 诱导 THP-1 细胞迁移/侵袭，以及 MMP-1、MMP-9 和 TIMP-1 的 mRNA 和蛋白表达。TIMP-2 的 mRNA 表达减少，TIMP-2 的蛋白表达不变。MMP-1/TIMP-1、MMP-1/TIMP-2、MMP-9/TIMP-1 和 MMP-9/TIMP-2 的比值增加。JNK、MEK/ERK、p38 MAPK 和 NF-κB 的抑制显著降低了 MMP/TIMP 比值，最终抑制了 THP-1 细胞的迁移/侵袭。这些发现表明，T. pallidum 诱导的 MMP/TIMP 失衡通过 MAPK 和 NF-κB 信号通路的激活增强了 THP-1 细胞的迁移和侵袭，这揭示了梅毒发病机制中的一个新步骤。
