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

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.

• Authors: Kaya Yoshida, Hirohiko Okamura, Yuka Hiroshima, Kaori Abe, Jun-Ichi Kido, Yasuo Shinohara, Kazumi Ozaki
• Journal: Experimental cell research (Exp Cell Res) Vol. 354 Issue 1 Pg. 57-64 (05 01 2017) ISSN: 1090-2422 [Electronic] United States
• PMID: 28341446 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Inflammasomes
• NF-kappa B
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, mouse
• PKR1 protein, mouse
• Receptors, G-Protein-Coupled
• Rela protein, mouse
• Transcription Factor RelA

Topics

• 3T3 Cells
• Animals
• Gene Expression Regulation (genetics)
• Humans
• Inflammasomes (genetics)
• Inflammation (genetics, microbiology, pathology)
• Mice
• NF-kappa B (genetics)
• NLR Family, Pyrin Domain-Containing 3 Protein (biosynthesis, genetics)
• Osteoblasts (metabolism, microbiology, pathology)
• Periodontal Pocket (genetics, microbiology)
• Porphyromonas gingivalis (genetics, pathogenicity)
• Receptors, G-Protein-Coupled (biosynthesis, genetics)
• Signal Transduction (genetics)
• Transcription Factor RelA (biosynthesis, genetics)