Yohei Yamaguchi1, Tomoko Kurita-Ochiai2, Ryoki Kobayashi3, Toshihiko Suzuki4, Tomohiro Ando1. 1. Department of Oral and Maxillofacial Surgery, School of Medicine, Tokyo Women's Medical University, Tokyo, Japan. 2. Department of Microbiology and Immunology, Nihon University School of Dentistry at Matsudo, Chiba, Japan. ochiai.tomoko@nihon-u.ac.jp. 3. Department of Microbiology and Immunology, Nihon University School of Dentistry at Matsudo, Chiba, Japan. 4. Department of Bacterial Pathogenesis, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Abstract
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.
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.
Authors: Mihai G Netea; Frank L van de Veerdonk; Jos W M van der Meer; Charles A Dinarello; Leo A B Joosten Journal: Annu Rev Immunol Date: 2014-12-10 Impact factor: 28.527
Authors: Ana Carolina de Faria Morandini; Carla Renata Sipert; Erivan Schnaider Ramos-Junior; Daniel Thomas Brozoski; Carlos Ferreira Santos Journal: Braz Oral Res Date: 2011 Mar-Apr
Authors: Matthew D McGeough; Carla A Pena; James L Mueller; Derek A Pociask; Lori Broderick; Hal M Hoffman; Susannah D Brydges Journal: J Immunol Date: 2012-08-17 Impact factor: 5.422