Porphyromonas gingivalis ATCC 33277 promotes intercellular adhesion molecule-1 expression in endothelial cells and monocyte-endothelial cell adhesion through macrophage migration inhibitory factor.

BACKGROUND: Porphyromonas gingivalis (P. gingivalis), one of the main pathogenic bacteria involved in periodontitis, induces the expression of intercellular adhesion molecule - 1 (ICAM-1) and monocyte-endothelial cell adhesion. This effect plays a pivotal role in atherosclerosis development. Macrophage migration inhibitory factor (MIF) is a multifunctional cytokine and critically affects atherosclerosis pathogenesis. In this study, we tested the involvement of MIF in the P. gingivalis ATCC 33277-enhanced adhesive properties of endothelial cells. RESULTS: Endothelial MIF expression was enhanced by P. gingivalis ATCC 33277 infection. The MIF inhibitor ISO-1 inhibited ICAM-1 production in endothelial cells, and monocyte-endothelial cell adhesion was induced by P. gingivalis ATCC 33277 infection. However, the addition of exogenous human recombinant MIF to P. gingivalis ATCC 33277-infected endothelial cells facilitated monocyte recruitment by promoting ICAM-1 expression in endothelial cells. CONCLUSIONS: These experiments revealed that MIF in endothelial cells participates in the pro-atherosclerotic lesion formation caused by P. gingivalis ATCC 33277 infection. Our novel findings identify a more detailed pathological role of P. gingivalis ATCC 33277 in atherosclerosis.

Porphyromonas gingivalis-Induced MIF Regulates Intercellular Adhesion Molecule-1 Expression in EA.hy926 Cells and Monocyte-Endothelial Cell Adhesion Through the Receptors CD74 and CXCR4.

Porphyromonas gingivalis (P. gingivalis) is an important pathogen that contributes to periodontal disease and causes infections that promote the progression of atherosclerosis. Our previous studies showed that macrophage migration inhibitory factor (MIF) facilitates monocyte adhesion to endothelial cells by regulating the expression of intercellular adhesion molecule-1 (ICAM-1) in P. gingivalis-infected endothelial cells. However, the detailed pathological role of MIF has yet to be elucidated in this context. To explore the functional receptor(s) of MIF that underlie its participation in the pathogenesis of atherosclerosis, we investigated the expression of the chemokine receptors CD74 and CXCR4 in endothelial cells, both of which were shown to be involved in the adhesion of monocytes to endothelial cells pretreated with P. gingivalis. Furthermore, the formation of a MIF, CD74, and CXCR4 ligand-receptor complex was revealed by our immunofluorescence staining and coimmunoprecipitation results. By interacting with the CD74/CXCR4 receptor complex, MIF may act as a crucial regulator of monocyte-endothelial cell adhesion and promote the atherosclerotic plaque formation induced by P. gingivalis.