2022 Fiscal Year Final Research Report

Dysfunction of the gingival epithelial barrier on the induction of neutrophil extracellular traps by periodontopathogenic bacteria

Research Project

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Project/Area Number	19K10143
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 57030:Conservative dentistry-related
Research Institution	Tohoku University
Principal Investigator	Tada Hiroyuki 東北大学, 歯学研究科, 講師 (70431632)
Co-Investigator(Kenkyū-buntansha)	西岡貴志東北大学, 歯学研究科, 講師 (50641875) 松下健二国立研究開発法人国立長寿医療研究センター, 研究所口腔疾患研究部, 部長 (90253898)
Project Period (FY)	2019-04-01 – 2023-03-31
Keywords	慢性歯周炎 / 歯周病原細菌 / Porphyromonas gingivalis / Fusobacterium nucleatum / 細胞外トラップ / 歯肉上皮バリア破綻
Outline of Final Research Achievements	In chronic periodontitis, periodontal tissue is destroyed by chronic inflammation caused by periodontopathogenic bacteria. This study investigated the mechanisms by which neutrophil extracellular traps (NETs) released by neutrophils in response to infection with periodontopathogenic bacteria disrupt the oral mucosal barrier and exacerbate periodontal disease. Fusobacterium nucleatum induced the release of NETs from neutrophils, which markedly expressed macrophage migration inhibitory factor. F. nucleatum also released the release of extracellular traps from mast cells, which in turn induced an inflammatory response in macrophages. On the other hand, gingipains, proteases produced by Porphyromonas gingivalis, degrades plasminogen activator inhibitor-1 (PAI-1) produced by endothelial cells and delayed wound healing in the vascular endothelium. These findings suggest that chronic inflammation caused by periodontopathogenic bacteria induces dysfunction of the oral mucosal barrier.
Free Research Field	口腔微生物学・免疫学
Academic Significance and Societal Importance of the Research Achievements	歯周病は、口のなかに常在する歯周病菌による感染症で、持続的な感染により引き起こされる慢性炎症が歯を支える顎の骨を破壊する。よって、慢性炎症のメカニズム解明は、歯周病の予防に重要な意味を持つ。本研究は、歯周病菌が慢性炎症を引き起こし、歯ぐきを支える粘膜バリアを破壊することを明らかにした。歯周病菌の感染に対して、免疫細胞の好中球やマスト細胞は細胞外トラップと呼ばれるクモの巣状の網を噴射し細菌を破壊するが、細胞外トラップは炎症も引き起こすことを明らかにした。また、歯周病菌の持つ酵素であるジンジパインは、血管の修復を遅延させることを明らかにした。