%0 Journal Article
%T Porphyromonas gingivalis Gingipains Trigger a Proinflammatory Response in Human Monocyte-derived Macrophages Through the p38¦Á Mitogen-activated Protein Kinase Signal Transduction Pathway
%A Daniel Grenier
%A Shin-ichi Tanabe
%J Toxins
%D 2010
%I MDPI AG
%R 10.3390/toxins2030341
%X 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-¦Á 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 p38¦Á 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.
%K P. gingivalis
%K proteinase
%K macrophage
%K cytokine
%K inflammation
%K p38¦Á MAPK
%U http://www.mdpi.com/2072-6651/2/3/341