title: Arginine-specific gingipain A from Porphyromonas gingivalis induces Weibel-Palade body exocytosis and enhanced activation of vascular endothelial cells through protease-activated receptors.
abstract: Gingipains, cysteine proteases derived from Porphyromonas gingivalis, are important virulence factors in periodontal diseases. We found that arginine-specific gingipain A (RgpA) increased the responsiveness of vascular endothelial cells to P. gingivalis lipopolysaccharides (LPS) and P. gingivalis whole cells to induce enhanced IL-8 production through protease-activated receptors (PARs) and phospholipase C (PLC) gamma. We therefore investigated whether RgpA-induced enhanced cell activation is mediated through exocytosis of Weibel-Palade bodies (WPBs) because they store vasoactive substances. RgpA rapidly activated PAR- and PLCgamma-dependent WPB exocytosis. In addition, angiopoietin (Ang)-2, a substance of WPB, enhanced IL-8 production by P. gingivalis LPS, suggesting that Ang-2 mediates the RgpA-induced enhanced cell responses. Thus, we propose a novel role for RgpA in induction of a proinflammatory event through PAR-mediated WPB exocytosis, which may be an important step for enhanced endothelial responses to P. gingivalis.
authors.affiliation: Department of Oral Disease Research, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, 36-3 Gengo, Morioka, Obu, Aichi 474-8522, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Inomata
authors.forename: Takeshi
authors.initials: T
authors.lastname: Into
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ishihara
authors.forename: Misako
authors.initials: M
authors.lastname: Nakashima
authors.forename: Toshihide
authors.initials: T
authors.lastname: Noguchi
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsushita
mesh_terms: D018829:Adhesins, Bacterial / Q000276:immunology*; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000276:immunology*; D042783:Endothelial Cells / Q000276:immunology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology*; D005089:Exocytosis / Q000502:physiology*; D000080867:Gingipain Cysteine Endopeptidases; D006801:Humans; D016966:Porphyromonas gingivalis / Q000276:immunology*; D044462:Receptors, Proteinase-Activated / Q000378:metabolism*; D014471:Umbilical Veins; D020302:Weibel-Palade Bodies / Q000502:physiology*
chemical_list: D018829:Adhesins, Bacterial; D000080867:Gingipain Cysteine Endopeptidases; D044462:Receptors, Proteinase-Activated; D003546:Cysteine Endopeptidases