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

Yicong Liu, Zhou Wu, Yurika Nakanishi, Junjun Ni, Yoshinori Hayashi, Fumiko Takayama, Yanmin Zhou, Tomoko Kadawaki, Hiroshi Nakanishi

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36 Citations (Scopus)

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.

Original languageEnglish
Article number11759
JournalScientific reports
Volume7
Issue number1
DOIs
Publication statusPublished - Dec 1 2017

All Science Journal Classification (ASJC) codes

  • General

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