Regulation of the NLRP3 inflammasome in Porphyromonas gingivalis-accelerated periodontal disease.
OBJECTIVE
Porphyromonas gingivalis is involved in the pathogenesis of chronic inflammatory periodontal disease. Recent studies have suggested that the NLRP3 inflammasome plays an important role in the development of chronic inflammation. We investigated a possible association between the inflammasome in gingival inflammation and bone loss induced by P. gingivalis infection using NLRP3-deficient mice.


METHODS
Wild-type and NLRP3-deficient mice were injected orally with P. gingivalis. We assessed alveolar bone loss, expression of pro-interleukin (IL)-1β, pro-IL-18, receptor activator of nuclear factor kappa-B ligand (RANKL), and osteoprotegerin (OPG) in gingival tissue, as well as IL-1β, IL-18, and IL-6 production and caspase-1 activity in peritoneal macrophages.


RESULTS
Porphyromonas gingivalis challenge significantly increased alveolar bone loss; gingival gene expression of pro-IL-1β, pro-IL-18, and RANKL; production of IL-1β, IL-18, and IL-6; and caspase-1 activity in peritoneal macrophages of wild-type mice, but did not affect NLRP3-deficient mice. Meanwhile, OPG mRNA expression in gingival tissue and peritoneal IL-6 production were significantly higher in NLRP3-knockout mice.


CONCLUSIONS
Porphyromonas gingivalis activated innate immune cells via the NLRP3 inflammasome. These results suggest that the NLRP3 inflammasome, followed by a response from the IL-1 family, is critical in periodontal disease induced by wild-type P. gingivalis challenge via sustained inflammation.
Department of Oral and Maxillofacial Surgery, School of Medicine, Tokyo Women's Medical University, Tokyo, Japan.
Yohei
Y
Yamaguchi
Department of Microbiology and Immunology, Nihon University School of Dentistry at Matsudo, Chiba, Japan. ochiai.tomoko@nihon-u.ac.jp.
Tomoko
http://orcid.org/0000-0002-9219-2315
T
Kurita-Ochiai
Department of Microbiology and Immunology, Nihon University School of Dentistry at Matsudo, Chiba, Japan.
Ryoki
R
Kobayashi
Department of Bacterial Pathogenesis, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Toshihiko
T
Suzuki
Department of Oral and Maxillofacial Surgery, School of Medicine, Tokyo Women's Medical University, Tokyo, Japan.
Tomohiro
T
Ando
D016301:Alveolar Bone Loss / Q000378:metabolism; D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005881:Gingiva / Q000378:metabolism; D058847:Inflammasomes / Q000235:genetics / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000235:genetics / Q000378:metabolism*; D053244:Osteoprotegerin / Q000235:genetics; D010510:Periodontal Diseases / Q000378:metabolism*; D016966:Porphyromonas gingivalis; D053245:RANK Ligand / Q000235:genetics
D016207:Cytokines; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D053244:Osteoprotegerin; D053245:RANK Ligand; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse
Inflammasome; NLRP3; Periodontal disease; Periodontopathic bacteria; Porphyromonas gingivalis
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