PKR induces the expression of NLRP3 by regulating the NF-κB pathway in Porphyromonas gingivalis-infected osteoblasts.
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.
Department of Oral Healthcare Education, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto, Tokushima 770-8504, Japan. Electronic address: kaya@tokushima-u.ac.jp.
Kaya
K
Yoshida
Department of Histology and Oral Histology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto, Tokushima 770-8504, Japan; Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata, Kita-ku, Okayama 770-8525, Japan.
Hirohiko
H
Okamura
Institute for Genome Research, Tokushima University, 3-18-15 Kuramoto, Tokushima 770-8503, Japan.
Yuka
Y
Hiroshima
SHIBASAKI, Inc., 507 Horikiri, Chichibu 368-0066, Japan.
Kaori
K
Abe
Department of Periodontology and Endodontology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto, Tokushima 770-8504, Japan.
Jun-Ichi
JI
Kido
Institute for Genome Research, Tokushima University, 3-18-15 Kuramoto, Tokushima 770-8503, Japan.
Yasuo
Y
Shinohara
Oral Healthcare Promotion, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto, Tokushima 770-8504, Japan.
Kazumi
K
Ozaki
D016475:3T3 Cells; D000818:Animals; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D058847:Inflammasomes / Q000235:genetics*; D007249:Inflammation / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D016328:NF-kappa B / Q000235:genetics; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000096:biosynthesis / Q000235:genetics*; D010006:Osteoblasts / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D010514:Periodontal Pocket / Q000235:genetics / Q000382:microbiology; D016966:Porphyromonas gingivalis / Q000235:genetics / Q000472:pathogenicity; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D051996:Transcription Factor RelA / Q000096:biosynthesis* / Q000235:genetics
D058847:Inflammasomes; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; C525015:PKR1 protein, mouse; D043562:Receptors, G-Protein-Coupled; C498144:Rela protein, mouse; D051996:Transcription Factor RelA
Double-stranded RNA-dependent kinase; Inflammasomes; NF-kappa B; Osteoblasts; Porphyromonas gingivalis