Int J Oral Biol.  2012 Sep;37(3):130-136.

Fusobacterium nucleatum GroEL signaling via Toll-like receptor 4 in human microvascular endothelial cells

• Lee HR
• Choi BK

Abstract

The GroEL heat-shock protein from Fusobacterium nucleatum, a periodontopathogen, activates risk factors for atherosclerosis in human microvascular endothelial cells (HMEC-1) and ApoE-/- mice. In this study, we analyzed the signaling pathways by which F. nucleatum GroEL induces the proinflammatory factors in HMEC-1 cells known to be risk factors associated with the development of atherosclerosis and identified the cellular receptor used by GroEL. The MAPK and NF-kappaB signaling pathways were found to be activated by GroEL to induce the expression of interleukin-8 (IL-8), monocyte chemoattractant protein 1 (MCP-1), intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), E-selectin, and tissue factor (TF). These effects were inhibited by a TLR4 knockdown. Our results thus indicate that TLR4 is a key receptor that mediates the interaction of F. nucleatum GroEL with HMEC-1 cells and subsequently induces an inflammatory response via the MAPK and NF-kappaB pathways.

Keyword

Fusobacterium nucleatum; GroEL; Periodontitis; Signaling

MeSH Terms

Animals
Atherosclerosis
Chemokine CCL2
E-Selectin
Endothelial Cells
Fusobacterium
Fusobacterium nucleatum
Heat-Shock Proteins
Humans
Intercellular Adhesion Molecule-1
Interleukin-8
Mice
NF-kappa B
Periodontitis
Risk Factors
Thromboplastin
Toll-Like Receptor 4
Toll-Like Receptors
Vascular Cell Adhesion Molecule-1
Chemokine CCL2
E-Selectin
Heat-Shock Proteins
Intercellular Adhesion Molecule-1
Interleukin-8
NF-kappa B
Thromboplastin
Toll-Like Receptor 4
Toll-Like Receptors
Vascular Cell Adhesion Molecule-1