Eikenella corrodens lipopolysaccharide stimulates the pro-atherosclerotic response in human coronary artery endothelial cells and monocyte adhesion

Viafara García, Sergio Marino; Gualtero, Diego Fernando; Avila‐Ceballos, Daniel; Lafaurie, Gloria Ines; Lafaurie, Gloria Ines [0000-0003-3986-0625]; Gualtero, Diego Fernando [0000-0002-6407-5605]; Viafara García, Sergio Marino [0000-0002-4208-1422]

Eikenella corrodens lipopolysaccharide stimulates the pro-atherosclerotic response in human coronary artery endothelial cells and monocyte adhesion | Eikenella corrodens lipopolysaccharide stimulates the pro-atherosclerotic response in human coronary artery endothelial cells and monocyte adhesion

2018

Eikenella corrodens is a gram‐negative bacterium, and although primarily associated with periodontal infections or infective endocarditis, it has been identified in coronary atheromatous plaques. The effect of its lipopolysaccharide (LPS) on human coronary artery endothelial cells (HCAECs) is unknown. Our aim was to examine the mechanism underlying the inflammatory response in HCAECs stimulated with E. corrodens‐LPS and to evaluate monocyte adhesion. Endothelial responses were determined by measuring the levels of chemokines and cytokines using flow cytometry. The surface expression of intercellular adhesion molecule 1 (ICAM‐1) was determined using a cell‐based ELISA, and the adhesion of THP‐1 monocytes to HCAECs was also monitored. The involvement of toll‐like receptors (TLRs) 2 and 4 was examined using TLR‐neutralizing antibodies, and activation of extracellular signal‐regulated kinase (ERK)1/2 and nuclear factor‐kappa B (NF‐κB) p65 were measured by western blotting and ELISA, respectively. Eikenella corrodens‐LPS increased secretion of interleukin‐8 (IL‐8), monocyte chemotactic protein 1 (MCP‐1), and granulocyte–macrophage colony‐stimulating factor (GM‐CSF), and expression of ICAM‐1 on the surface of HCAECs, consistent with the increased adhesion of THP‐1 cells. Moreover, E. corrodens‐LPS interacted with TLR4, a key receptor able to maintain the levels of IL‐8, MCP‐1, and GM‐CSF in HCAECs. Phosphorylation of ERK1/2 and activation of NF‐κB p65 were also increased. The results indicate that E. corrodens‐LPS activates HCAECs through TLR4, ERK, and NF‐κB p65, triggering a pro‐atherosclerotic endothelial response and enhancing monocyte adhesion.

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