Chemerin Induced by Treponema pallidum Predicted Membrane Protein Tp0965 Mediates Endothelial Dysfunction via Activating MAPK Signaling Pathway

Chemerin, a chemoattractant protein, is involved in endothelial dysfunction and vascular inflammation in pathological conditions. In a recent study, we observed the upregulation of chemerin in endothelial cells following in vitro treatment with T. pallidum . Here, we investigated the role of chemerin in endothelial cells dysfunction induced by the T. pallidum predicted membrane protein Tp0965. Following stimulation of human umbilical vein endothelial cells (HUVECs) with Tp0965, chemerin and its ChemR23 receptor were up-regulated, companied with elevated expression of TLR2. Furthermore, chemerin from HUVECs activated endothelial cells via chemerin/ChemR23 signaling in an autocrine/paracrine manner, characterized by upregulated expression of ICAM-1, E-selectin and MMP-2. Activation of endothelial cells depended on the MAPK signaling pathway. In addition, Tp0965-induced chemerin promoted monocytes migration to endothelial cells, also via chemerin/ChemR23 pathway. The RhoA/ROCK signaling pathway was also involved in monocytes migration in response to chemerin/ChemR23. Our results highlight the role of Tp0965-induced chemerin in endothelial cells dysfunction, which contributes to the immunopathogenesis of vascular inflammation of syphilis. Author summary Treponema pallidum is the spirochete of syphilis, which causes a chronic system inflammation. Endothelium damage caused by this bacterium is the key step in the systemic dissemination and pathophysiology of syphilis, particularly cardiovascular syphilis and neurosyphilis. In this study, we show a novel molecular mechanism of endothelium damage induce by Treponema pallidum predicted membrane protein Tp0965. Chemerin is a recently identified adipocytokine and chemoattractant protein with a crucial role in endothelial dysfunction and vascular inflammation in pathological conditions. Our data show that Tp0965 up-regulated the expression of chemerin and its ChemR23 receptor by endothelial cells in vitro. Furthermore, chemerin from HUVECs activated endothelial cells via chemerin/ChemR23 signaling in an autocrine/paracrine manner and depended on the MAPK signaling pathway. In addition, Tp0965-induced chemerin promoted monocytes migration to endothelial cells, also via chemerin/ChemR23 pathway. The RhoA/ROCK signaling pathway was also involved in monocytes migration in response to chemerin/ChemR23. These findings contribute to the immunopathogenesis of vascular inflammation of syphilis.