title: Porphyromonas gingivalis gingipains trigger a proinflammatory response in human monocyte-derived macrophages through the p38α mitogen-activated protein kinase signal transduction pathway.
abstract: Porphyromonas gingivalis, the major etiologic agent of chronic periodontitis, produces a broad spectrum of virulence factors, including Arg- and Lys-gingipain cysteine proteinases. In this study, we investigated the capacity of P. gingivalis gingipains to trigger a proinflammatory response in human monocyte-derived macrophages. Both Arg- and Lys-gingipain preparations induced the secretion of TNF-α and IL-8 by macrophages. Stimulation of macrophages with Arg-gingipain A/B preparation at the highest concentration was associated with lower amounts of cytokines detected, a phenomenon likely related to proteolytic degradation. The inflammatory response induced by gingipains was not dependent of their catalytic activity since heat-inactivated preparations were still effective. Stimulating macrophages with gingipain preparations was associated with increased levels of phosphorylated p38α MAPK suggesting its involvement in cell activation. In conclusion, our study brought clear evidence that P. gingivalis Arg- and Lys-gingipains may contribute to the host inflammatory response, a critical factor in periodontitis-associated tissue destruction.
authors: Groupe de Recherche en Écologie Buccale, Faculté de Médecine Dentaire, Université Laval, Quebec City, Quebec. daniel.grenier@greb.ulaval.ca
authors: Daniel
authors: D
authors: Grenier
authors: Shin-Ichi
authors: S
authors: Tanabe
mesh_terms: D018829:Adhesins, Bacterial / Q000302:isolation & purification / Q000494:pharmacology*; D045424:Complex Mixtures / Q000737:chemistry; D003546:Cysteine Endopeptidases / Q000302:isolation & purification / Q000494:pharmacology*; D000080867:Gingipain Cysteine Endopeptidases; D006801:Humans; D016209:Interleukin-8 / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D048308:Mitogen-Activated Protein Kinase 14 / Q000276:immunology*; D016966:Porphyromonas gingivalis; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D020298:U937 Cells
chemical_list: D018829:Adhesins, Bacterial; D045424:Complex Mixtures; D000080867:Gingipain Cysteine Endopeptidases; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D048308:Mitogen-Activated Protein Kinase 14; D003546:Cysteine Endopeptidases