Examination of biological response to Porphyromonas gingivalis infection.

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Porphyromonas gingivalis is the primary pathogenic agent of adult periodontitis and produces a unique class of virulence proteinases known as Arg-gingipains (Rgps) and Lys-gingipain (Kgp). We purified a 660-kDa cell-associated gingipain complex existing as a homodimer of two catalytically active monomers that comprises their catalytic and adhesin domains. Electron microscopy revealed that the complex was composed of a globular particle with 10-nm external diameter possessing one or two electron dense hole-like structures. Two-dimensional gel electrophoresis and immunoblot analyses revealed the complex includes lipopolysaccharide (LPS). The complex significantly degraded human type I collagen and elastin and strongly disrupted cell viability of human gingival fibroblasts and endotherial cells with higher efficiencies compared to the monomeric gingipains. The native complex little induced production of nitrogen dioxide (NO_2), tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) b … More y macrophages, whereas the heat-denatured complex resulted in increased production of them. The results indicate the importance of the complex in evasion of host defense mechanisms as well as in host tissue breakdown. Many epidemiological studies suggest that periodontal infections are a risk factor for atherosclerosis. Repeated intravenous injection of wild-type P.gingivalis resulted in an increase in the area of atherosclerotic lesions as well as an increase in the serum concentration of low-density lipoprotein (LDL) cholesterol and a decrease in that of high-density lipoprotein (HDL) cholesterol in apolipoprotein (apo) E-knockout mice fed a high-fat diet. However, Rgp/Kgp-deficient P.gingivalis did not promoted the atherosclerotic lesions. The specific inhibitors against Rgp suppressed the promotion of atherosclerotic lesions induced by wild-type P.gingivalis. Proteolytic activity of Rgp thus appears to play a crucial role in the promotion of atherosclerosis by P.gingivalis infection. Less