Porphyromonas gingivalis-mediated shedding of extracellular matrix metalloproteinase inducer (EMMPRIN) by oral epithelial cells: A potential role in inflammatory periodontal disease

Mark Feldman, Vu Dang La, Telma Blanca Lombardo Bedran, Denise Madalena Palomari Spolidorio, Daniel Grenier*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Extracellular matrix metalloproteinase inducer (EMMPRIN) or CD147 is a transmembrane glycoprotein expressed by various cell types, including oral epithelial cells. Recent studies have brought evidence that EMMPRIN plays a role in periodontitis. In the present study, we investigated the effect of Porphyromonas gingivalis, a major pathogen in chronic periodontitis, on the shedding of membrane-anchored EMMPRIN and on the expression of the EMMPRIN gene by oral epithelial cells. A potential contribution of shed EMMPRIN to the inflammatory process of periodontitis was analyzed by evaluating the effect of recombinant EMMPRIN on cytokine and matrix metalloproteinase (MMP) secretion by human gingival fibroblasts. ELISA and immunofluorescence analyses revealed that P. gingivalis mediated the shedding of epithelial cell-surface EMMPRIN in a dose- and time-dependent manner. Cysteine proteinase (gingipain)-deficient P. gingivalis mutants were used to demonstrate that both Arg- and Lys-gingipain activities are involved in EMMPRIN shedding. Real-time PCR showed that P. gingivalis had no significant effect on the expression of the EMMPRIN gene in epithelial cells. Recombinant EMMPRIN induced the secretion of IL-6 and MMP-3 by gingival fibroblasts, a phenomenon that appears to involve mitogen activated protein kinases. The present study brought to light a new mechanism by which P. gingivalis can promote the inflammatory response during periodontitis.

Original languageAmerican English
Pages (from-to)1261-1269
Number of pages9
JournalMicrobes and Infection
Volume13
Issue number14-15
DOIs
StatePublished - Dec 2011
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by the Canadian Institutes of Health Research . We would like to thank Koji Nakayama (Nagasaki University) for providing the gingipain-deficient mutants and Valerie Murrah (University of North Carolina at Chapel Hill) for providing the GMSM-K cell line.

Keywords

  • Cytokine
  • EMMPRIN
  • Epithelial cell
  • Fibroblast
  • Periodontitis
  • Porphyromonas gingivalis

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