Infection of microglia with Porphyromonas gingivalis promotes cell migration and an inflammatory response through the gingipain-mediated activation of protease-activated receptor-2 in mice

Sci Rep. 2017 Sep 18;7(1):11759. doi: 10.1038/s41598-017-12173-1.

Abstract

Despite a clear correlation between periodontitis and cognitive decline in Alzheimer's disease, the precise mechanism underlying the relationship remains unclear. The periodontal pathogen Porphyromonas gingivalis produces a unique class of cysteine proteinases termed gingipains that comprises Arg-gingipain (Rgp) and Lys-gingipain (Kgp). Rgp and Kgp are important in the bacterial mediated host cell responses and the subsequent intracellular signaling in infected cells. In the present study, we attempted to clarify the potential effects of Rgp and Kgp on the cellular activation of brain-resident microglia. We provide the first evidence that Rgp and Kgp cooperatively contribute to the P. gingivalis-induced cell migration and expression of proinflammatory mediators through the activation of protease-activated receptor 2. The subsequent activation of phosphoinositide 3-kinase/Akt and mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase/ERK pathways contributes to cell migration and inflammatory response of microglia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteroidaceae Infections / genetics
  • Bacteroidaceae Infections / metabolism*
  • Bacteroidaceae Infections / pathology
  • Cell Movement*
  • Cysteine Endopeptidases / metabolism*
  • Extracellular Signal-Regulated MAP Kinases
  • Gingipain Cysteine Endopeptidases
  • MAP Kinase Signaling System*
  • Mice
  • Mice, Transgenic
  • Microglia / metabolism*
  • Microglia / microbiology
  • Phosphatidylinositol 3-Kinases
  • Porphyromonas gingivalis / metabolism*
  • Porphyromonas gingivalis / pathogenicity
  • Proto-Oncogene Proteins c-akt
  • Receptor, PAR-2 / genetics
  • Receptor, PAR-2 / metabolism*

Substances

  • Gingipain Cysteine Endopeptidases
  • Receptor, PAR-2
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases
  • Cysteine Endopeptidases