Porphyromonas gingivalisFimbria-Dependent Activation of Inflammatory Genes in Human Aortic Endothelial Cells

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Abstract
Epidemiological and pathological studies have suggested that infection with the oral pathogenPorphyromonas gingivaliscan potentiate atherosclerosis and human coronary heart disease. Furthermore, infection with invasive, but not noninvasiveP. gingivalishas been demonstrated to accelerate atherosclerosis in apolipoprotein E-deficient (ApoE−/−) mice and to accelerate local inflammatory responses in aortic tissue. In the present study, using high-density oligonucleotide microarrays, we have defined the gene expression profile of human aortic endothelial cells (HAEC) after infection with invasive and noninvasiveP. gingivalis. After infection of HAEC with invasiveP. gingivalisstrain 381, we observed the upregulation of 68 genes. Genes coding for the cytokines Gro2 and Gro3; the adhesion molecules intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule (VCAM)-1, and ELAM-1 (E-selectin); the chemokine interleukin-8 (IL-8); and the proinflammatory molecules IL-6 and cyclooxygenase-2 were among the most highly upregulated genes inP. gingivalis381-infected HAEC compared to uninfected HAEC control. Increased mRNA levels for signaling molecules, transcriptional regulators, and cell surface receptors were also observed. Of note, only 4 of these 68 genes were also upregulated in HAEC infected with the noninvasiveP. gingivalis fimAmutant. Reverse transcription-PCR, enzyme-linked immunosorbent assay, and fluorescence-activated cell sorting analysis confirmed the expression of ICAM-1, VCAM-1, E-/P-selectins, IL-6, and IL-8 in HAEC infected with invasiveP. gingivalis. We also demonstrated that increased expression of ICAM-1 and VCAM-1 in aortic tissue of ApoE−/−mice orally challenged with invasiveP. gingivalisbut not with the noninvasiveP. gingivalis fimAmutant by immunohistochemical analysis. Taken together, these results demonstrate thatP. gingivalisfimbria-mediated invasion upregulates inflammatory gene expression in HAEC and in aortic tissue and indicates that invasiveP. gingivalisinfection accelerates inflammatory responses directly in the aorta.