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Toxins 2010, 2(3), 341-352; doi:10.3390/toxins2030341

Porphyromonas gingivalis Gingipains Trigger a Proinflammatory Response in Human Monocyte-derived Macrophages Through the p38α Mitogen-activated Protein Kinase Signal Transduction Pathway

Groupe de Recherche en Écologie Buccale, Faculté de Médecine Dentaire, Université Laval, 2420 de la Terrasse, Quebec City, Quebec, G1V 0A6, Canada
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Received: 8 February 2010 / Revised: 4 March 2010 / Accepted: 8 March 2010 / Published: 10 March 2010
(This article belongs to the Special Issue Protein Toxins as Proteases)
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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. View Full-Text
Keywords: P. gingivalis; proteinase; macrophage; cytokine; inflammation; p38α MAPK P. gingivalis; proteinase; macrophage; cytokine; inflammation; p38α MAPK
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MDPI and ACS Style

Grenier, D.; Tanabe, S.-I. Porphyromonas gingivalis Gingipains Trigger a Proinflammatory Response in Human Monocyte-derived Macrophages Through the p38α Mitogen-activated Protein Kinase Signal Transduction Pathway. Toxins 2010, 2, 341-352.

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