LOX-1 Regulates P. gingivalis-Induced Monocyte Migration and Adhesion to Human Umbilical Vein Endothelial Cells.

Qian Li,Jianru Liu,Jinsheng Zhong,Xiangying Ouyang,Yi Chu,Ying Xie,Xinzhe Lou,Wenyi Liu

doi:10.3389/fcell.2020.00596

Abstract

Porphyromonas gingivalis (P. gingivalis) is one of the main periodontal bacteria. This pathogen was reported to enhance monocyte migration and adhesion to endothelial cells in atherosclerosis. The scavenger receptor lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) plays a pivotal role in atherogenesis. The aim of this study was to investigate whether LOX-1 modulates P. gingivalis-mediated monocyte migration and adhesion to endothelial cells and how it works. The results showed that the migration and adhesion of monocytic THP-1 cells to human umbilical vein endothelial cells (HUVECs) were significantly enhanced when HUVECs or THP-1 cells were challenged with P. gingivalis. Meanwhile, the expression level of LOX-1 in both HUVECs and THP-1 cells were also significantly increased by P. gingivalis stimulation. It is well known that ligand/receptor pairs monocyte chemoattractant protein-1 (MCP-1)/CC chemokine receptor 2 (CCR2), selectins/Integrins, and cell adhesion molecules (CAMs)/Integrins mediate monocyte migration and adhesion to endothelial cells. In this study, LOX-1 was demonstrated to be crucially involved in P. gingivalis-induced THP-1 cell migration and adhesion to HUVECs, by regulating expression of ligands MCP-1, intercellular adhesion molecule-1 (ICAM-1) and E-selectin in HUVECs and that of their receptors CCR2 and Integrin αMβ2 in THP-1 cells. The nuclear factor-kappa B (NF-κB) signaling pathway was proved to be involved in this process. In conclusion, LOX-1 plays a crucial role in P. gingivalis-induced monocyte migration and adhesion to endothelial cells. This result implies LOX-1 may act as a bridge in linking periodontitis to atherosclerosis.

Highlights

Atherosclerosis is the major etiology of cardiovascular disease, the leading cause of mortality worldwide (Mayer and Binder, 2019)
When Human umbilical vein endothelial cells (HUVECs) were challenged with P. gingivalis for 24 h, the number of THP-1 cells migrated to the HUVECs markedly increased approximately 4.8-fold (Figure 1A), and the number of THP-1 cells adhered to the HUVECs increased approximately 7-fold (Figure 1B)
The number of THP-1 cells that migrated and adhered to HUVECs increased approximately 3.4fold (Figure 1C) and 8-fold (Figure 1D), respectively. These data demonstrate that the migration and adhesion of THP-1 cells to HUVECs are promoted by P. gingivalis

Summary

Introduction

Atherosclerosis is the major etiology of cardiovascular disease, the leading cause of mortality worldwide (Mayer and Binder, 2019). Endothelial cells express various inflammatory molecules when they are activated by kinds of stimuli such as low-density lipoprotein, hyperlipidemia, low shear stress, and TNF-α (Mestas and Ley, 2008). These inflammatory molecules interact with their receptors expressed in monocytes to mediate the recruitment, retention and firm adhesion of circulating monocytes. The expression of MCP-1, selectins, CAMs and their receptors is extremely crucial for monocyte migration and adhesion to endothelial cells. After migrating and adhering to endothelial cells, monocytes would emigrate into the intima and become lipid-laden macrophages, which contribute to the formation of atherosclerotic plaques (Jaipersad et al, 2014)

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