PKR induces the expression of NLRP3 by regulating the NF-κB pathway in Porphyromonas gingivalis-infected osteoblasts

Kaya Yoshida, Hirohiko Okamura, Yuka Hiroshima, Kaori Abe, Jun ichi Kido, Yasuo Shinohara, Kazumi Ozaki

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The double-stranded RNA-dependent kinase (PKR), which is activated by double stranded RNA, induces inflammation by regulating NF-κB signaling. The NLR family pyrin domain-containing 3 (NLRP3) inflammasome also modulates inflammation in response to infection. Porphyromonas gingivalis (P.gingivalis) is an oral bacterium which is implicated in the pathogenesis of periodontal diseases. We previously reported that PKR is a key modulator of bone metabolism and inflammation in the periodontal tissue. PKR was also reported to induce inflammation in response to microbes by regulating the NLRP3 inflammasome, suggesting that PKR could affect inflammation along with NLRP3 in periodontal diseases. In this study, we investigated the effects of PKR on NLRP3 expression and NF-κB activity in P. gingivalis infected osteoblasts. We first constructed a SNAP26b-tagged P.gingivalis (SNAP-P. g.) and traced its internalization into the cell. SNAP-P. g. increased the activity of PKR and NF-κB and also induced NLRP3 expression in osteoblasts. Inhibition of NF-κB attenuated SNAP-P. g.-induced NLRP3 expression. The knockdown of PKR using shRNA decreased both the activity of NF-κB and the expression of NLRP3 induced by SNAP-P.g. We therefore concluded that in osteoblasts, P. gingivalis activated PKR, which in turn increased NLRP3 expression by activating NF-κB. Our results suggest that PKR modulates inflammation by regulating the expression of the NLRP3 inflammasome through the NF-κB pathway in periodontal diseases.

Original languageEnglish
Pages (from-to)57-64
Number of pages8
JournalExperimental Cell Research
Volume354
Issue number1
DOIs
Publication statusPublished - May 1 2017

Fingerprint

Porphyromonas gingivalis
Osteoblasts
Inflammasomes
Inflammation
Periodontal Diseases
Double-Stranded RNA
Osteitis
Small Interfering RNA
Phosphotransferases
Bacteria
Infection

Keywords

  • Double-stranded RNA-dependent kinase
  • Inflammasomes
  • NF-kappa B
  • Osteoblasts
  • Porphyromonas gingivalis

ASJC Scopus subject areas

  • Cell Biology

Cite this

PKR induces the expression of NLRP3 by regulating the NF-κB pathway in Porphyromonas gingivalis-infected osteoblasts. / Yoshida, Kaya; Okamura, Hirohiko; Hiroshima, Yuka; Abe, Kaori; Kido, Jun ichi; Shinohara, Yasuo; Ozaki, Kazumi.

In: Experimental Cell Research, Vol. 354, No. 1, 01.05.2017, p. 57-64.

Research output: Contribution to journalArticle

Yoshida, Kaya ; Okamura, Hirohiko ; Hiroshima, Yuka ; Abe, Kaori ; Kido, Jun ichi ; Shinohara, Yasuo ; Ozaki, Kazumi. / PKR induces the expression of NLRP3 by regulating the NF-κB pathway in Porphyromonas gingivalis-infected osteoblasts. In: Experimental Cell Research. 2017 ; Vol. 354, No. 1. pp. 57-64.
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