Chemerin induced by Treponema pallidum predicted membrane protein Tp0965 mediates the activation of endothelial cell via MAPK signaling pathway

Abstract

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 Treponema pallidum. Here, we investigated the role of chemerin in endothelial cells activation induced by the T. pallidum predicted membrane protein Tp0965. Following stimulation of human umbilical vein endothelial cells (HUVECs) with Tp0965, chemerin and its receptor chemerin receptor 23 (ChemR23) were upregulated, companied with elevated expression of Toll-like receptor 2. Furthermore, chemerin from HUVECs activated endothelial cells via chemerin/ChemR23 signaling in an autocrine/paracrine manner, characterized by upregulated expression of intercellular adhesion molecule 1, E-selectin, and matrix metalloproteinase-2. Activation of endothelial cells depended on the mitogen-activated protein kinase signaling pathway. In addition, Tp0965induced chemerin promoted THP-1-derived macrophages migration to endothelial cells, also via the chemerin/ChemR23 pathway. The RhoA/ROCK signaling pathway was also involved in THP-1-derived macrophages migration in response to chemerin/ChemR23. Our results highlight the role of Tp0965induced chemerin in endothelial cells dysfunction, which contributes to the immunopathogenesis of vascular inflammation of syphilis. K E Y W O R D S chemerin, endothelial cell, membrane protein, syphilis, Treponema pallidum

Gene Expression Profiling in Human Brain Microvascular Endothelial Cells in Response to Treponema pallidum Subspecies pallidum

“…It is emphasized that the inflammatory response is responsible for syphilis pathogenesis during the invasion and persistence of T. pallidum. By recruiting immune cells to sites of tissue damage, vasculitis invokes and ultimately leads to T. pallidum dissemination by destroying the endothelial barrier, dependent on the activation of the RhoA/ROCK and MAPK signaling pathways (Zhang et al 2019). Our previous studies found that recombinant Treponema pallidum protein 17 (rTp 17) increased the expression of the gene encoding monocyte chemoattractant protein-1 (MCP-1) in HUVECs (Zhang et al 2015).…”

The complex role of adipokines in obesity, inflammation, and autoimmunity

“…The DCs then produce type I interferons, leading to proinflammatory polarization of adipose tissue-resident macrophages [194]. Monocyte-derived macrophages also express CMKLR1, and chemerin similarly promotes macrophage migration [195,196]. Herova et al determined that CMKLR1 is only expressed on M1 macrophages, but not M2 macrophages, indicating that the receptor is involved in recruitment of M1 macrophages to inflamed tissues [197].…”

Possible effects of Treponema pallidum infection on human vascular endothelial cells

“…Tp0965 can stimulate the expression mRNA and protein of ICAM‐1, E‐selectin, and monocyte chemotactic protein‐1 (MCP‐1) of HUVEC, and decrease the Claudin‐1 expression level of the tight junction protein, leading to increased vascular endothelial cell permeability, which further assists T. pallidum in crossing the vascular endothelium 22 . Recent research results have highlighted that Tp0965 induced Chemerin in endothelial cell dysfunction, which may be involved in the immune pathogenesis of vascular inflammation of syphilis 27 …”

“… 22 Recent research results have highlighted that Tp0965 induced Chemerin in endothelial cell dysfunction, which may be involved in the immune pathogenesis of vascular inflammation of syphilis. 27 …”