title: Activation of the NLRP3 inflammasome in Porphyromonas gingivalis-accelerated atherosclerosis.
abstract: Porphyromonas gingivalis has been shown to accelerate atherosclerotic lesion development in hyperlipidemic animals. Atherosclerosis is a disease characterized by inflammation of the arterial wall. Recent studies have suggested that the NLRP3 inflammasome plays an important role in the development of vascular inflammation and atherosclerosis. Herein, we investigated a possible association between the inflammasome in atherosclerosis and periodontal disease induced by P. gingivalis infection using apolipoprotein E-deficient, spontaneously hyperlipidemic (Apoe(shl)) mice. Oral infection with wild-type (WT) P. gingivalis significantly increased the area of aortic sinus covered with atherosclerotic plaque and alveolar bone loss, compared with KDP136 (gingipain-null mutant) or KDP150 (FimA-deficient mutant) challenge. WT challenge also increased IL-1β, IL-18 and TNF-α production in peritoneal macrophages, and gingival or aortic gene expression of Nod-like receptor family, pyrin domain containing 3 (NLRP3), pro-IL-1β, pro-IL-18 and pro-caspase-1. Porphyromonas gingivalis genomic DNA was detected more in the aorta, gingival tissue, liver and spleen of WT-challenged mice than those in KDP136- or KDP150-challenged mice. We conclude that WT P. gingivalis activates innate immune cells through the NLRP3 inflammasome compared with KDP136 or KDP150. The NLRP3 inflammasome may play a critical role in periodontal disease and atherosclerosis induced by P. gingivalis challenge through sustained inflammation.
authors: Department of Oral and Maxillofacial Surgery, Tokyo Women's Medical University, School of Medicine, Tokyo 162-8666, Japan.
authors: Yohei
authors: Y
authors: Yamaguchi
authors: Department of Microbiology and Immunology, Nihon University School of Dentistry at Matsudo, Chiba 271-8587, Japan ochiai.tomoko@nihon-u.ac.jp.
authors: Tomoko
authors: T
authors: Kurita-Ochiai
authors: Department of Microbiology and Immunology, Nihon University School of Dentistry at Matsudo, Chiba 271-8587, Japan.
authors: Ryoki
authors: R
authors: Kobayashi
authors: Department of Molecular Bacteriology and Immunology, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan.
authors: Toshihiko
authors: T
authors: Suzuki
authors: Department of Oral and Maxillofacial Surgery, Tokyo Women's Medical University, School of Medicine, Tokyo 162-8666, Japan.
authors: Tomohiro
authors: T
authors: Ando
mesh_terms: D016301:Alveolar Bone Loss; D000818:Animals; D050197:Atherosclerosis / Q000382:microbiology* / Q000473:pathology*; D002352:Carrier Proteins / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D058847:Inflammasomes / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010510:Periodontal Diseases / Q000382:microbiology / Q000473:pathology; D016966:Porphyromonas gingivalis / Q000276:immunology*; D012850:Sinus of Valsalva / Q000473:pathology
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human
keywords: NLRP3 inflammasome; Porphyromonas gingivalis; atherosclerosis