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A strategic approach to elucidate the etiology of EBV-induced periodontitis and to develop novel therapies

Research Project

Project/Area Number 19K10078
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57020:Oral pathobiological science-related
Research InstitutionNihon University

Principal Investigator

IMAI Kenichi  日本大学, 歯学部, 教授 (60381810)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsEBウイルス / 歯周病 / 炎症性サイトカイン / 破骨細胞 / 唾液 / EBV / ウイルス / 根尖性歯周炎 / BZLF1 / LMP1 / 歯周疾患
Outline of Research at the Start

世界で最も罹患者が多い感染症である歯周病は、歯を失う最大の要因である。歯周病が糖尿病や肺炎の発症に深く関与していることも明らかとなり、歯周病対策はますます重要となる。しかし、その病因は未だ解明されていない。
近年、新たな病原因子としてEBウイルス(EBV)の関与が世界的に注目されている。本研究では、臨床・基礎研究の推進と、ヒトの免疫系を有する特殊なマウスを用いた感染実験を遂行することで、新たな診断基準の基となる病因論の提示とEBVを標的とした新規予防・治療法のための分子基盤構築を目指す。国民の健康増進と健康寿命の延伸、さらには高騰する医療費削減に繋がることが期待できる。

Outline of Final Research Achievements

Periodontitis is an inflammatory condition that causes the destruction of the supporting tissues of teeth and is a major public health problem. Although traditional microbiological research on the etiology of periodontitis has focused on some oral endogenous bacteria, emerging evidence suggests an association between EBV and periodontitis progression. However, EBV’s role in the etiology of periodontitis is unknown. We found that extremely high levels of IL-6 and IL-8 were induced by inactivated EBV in a copy-dependent manner in HGFs. EBV induced IκBα degradation, NF-κB transcription, and RAW264.7 cell differentiation into osteoclast-like cells. Futhermore, BZLF1 mRNA expression and transcriptional activity in Daudi cells were induced only when treated with the hronic periodontitis patients' saliva. Thus, EBV, as well as periodontopathic bacteria, should be considered as a causative agent of the progression of human chronic periodontitis.

Academic Significance and Societal Importance of the Research Achievements

わが国では今後ますます高齢化が進むため、重症度のより高い患者の増加が見込まれる。また、歯周病がその発症に関与する糖尿病や肺炎等への影響も懸念される。長年にわたり、ある種の細菌と歯周疾患に関する研究が行われてきたが、未だに病因ははっきりしていない。最近、患部には細菌のみならず多くのEBウイルス(EBV)が存在することがわかってきた。EBVによる歯周疾患発症のメカニズムに関する研究は、新たな診断基準の基となる病因論の解明と新規治療法の開発に繋がることが期待される。また、EBVが関与するリンパ腫や胃がん、潰瘍性大腸炎など他の重要な疾患の研究に新たな情報を提示できる可能性もある。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (35 results)

All 2022 2021 2020 2019 Other

All Journal Article (18 results) (of which Peer Reviewed: 17 results,  Open Access: 15 results) Presentation (14 results) (of which Int'l Joint Research: 3 results,  Invited: 5 results) Book (1 results) Remarks (2 results)

  • [Journal Article] Epstein-Barr Virus Promotes the Production of Inflammatory Cytokines in Gingival Fibroblasts and RANKL-Induced Osteoclast Differentiation in RAW264.7 Cells.2022

    • Author(s)
      Yokoe S, Hasuike A, Watanabe N, Tanaka H, Karahashi H, Wakuda S, Takeichi O, Kawato T, Takai H, Ogata Y, Sato S, Imai K
    • Journal Title

      Int J Mol Sci.

      Volume: 23(2) Issue: 2 Pages: 80-80

    • DOI

      10.3390/ijms23020809

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fusobacterium nucleatum exacerbates chronic obstructive pulmonary disease in elastase-induced emphysematous mice.2022

    • Author(s)
      Suzuki R, Kamio N, Kaneko T, Yonehara Y, Imai K.
    • Journal Title

      FEBS Open Bio.

      Volume: 12(3) Issue: 3 Pages: 638-648

    • DOI

      10.1002/2211-5463.13369

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Porphyromonas gingivalis Mfa1 fimbria putatively binds to TLR2 and induces both IL-6 and IL-8 production in human bronchial epithelial cells.2022

    • Author(s)
      Takahashi Y, Cueno ME, Kamio N, Iinuma T, Hasegawa T, Imai K
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 589 Pages: 35-40

    • DOI

      10.1016/j.bbrc.2021.12.003

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Relationship between the oral cavity and respiratory diseases: Aspiration of oral bacteria possibly contributes to the progression of lower airway inflammation.2021

    • Author(s)
      Imai K, Iinuma T, Sato S.
    • Journal Title

      Jap. Dent. Sci. Rev.

      Volume: 53 Pages: 224-230

    • DOI

      10.1016/j.jdsr.2021.10.003

    • NAID

      210000172915

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 口腔と全身疾患研究の最前線 はじめに2021

    • Author(s)
      今井健一
    • Journal Title

      医学のあゆみ

      Volume: 277(12) Pages: 1009-1010

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Aspiration of periodontopathic bacteria due to poor oral hygiene potentially contributes to the aggravation of COVID-192021

    • Author(s)
      Takahashi Y, Watanabe N, Kamio N, Kobayashi R, Iinuma T, Imai K
    • Journal Title

      Journal of Oral Science

      Volume: 63 Issue: 1 Pages: 1-3

    • DOI

      10.2334/josnusd.20-0388

    • NAID

      130007959227

    • ISSN
      1343-4934, 1880-4926
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Analysis of the Interaction Between HIV and Periodontopathic Bacteria That Reactivates HIV Replication in Latently Infected Cells.2021

    • Author(s)
      Imai K.
    • Journal Title

      Methods Mol Biol.

      Volume: 2210 Pages: 207-214

    • DOI

      10.1007/978-1-0716-0939-2_20

    • ISBN
      9781071609385, 9781071609392
    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Expression of the SARS-CoV-2 Receptor ACE2 and Proinflammatory Cytokines Induced by the Periodontopathic Bacterium Fusobacterium nucleatum in Human Respiratory Epithelial Cells2021

    • Author(s)
      Takahashi Y, Watanabe N, Kamio N, Yokoe S, Suzuki R, Sato S, Iinuma T, Imai K
    • Journal Title

      Int J Mol Sci.

      Volume: 22(3) Issue: 3 Pages: 1352-1352

    • DOI

      10.3390/ijms22031352

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Structural Comparison of the SARS CoV 2 Spike Protein Relative to Other Human-Infecting Coronaviruses2021

    • Author(s)
      Cueno ME, Imai K
    • Journal Title

      Front Medicine

      Volume: 7 Pages: 594439-594439

    • DOI

      10.3389/fmed.2020.594439

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Insights on the structural variations of the furin-like cleavage site found among the December, 2019-July, 2020 SARS-CoV-2 spike glycoprotein: A computational study linking viral evolution and infection.2021

    • Author(s)
      Cueno ME, Ueno M, Iguchi R, Harada T, Miki Y, Yasumaru K, Kiso N, Wada K, Baba K, Imai K.
    • Journal Title

      Front Medicine

      Volume: 8 Pages: 613412-613412

    • DOI

      10.3389/fmed.2021.613412

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Porphyromonas gingivalis enhances pneumococcal adhesion to human alveolar epithelial cells by increasing expression of host platelet-activating factor receptor.2021

    • Author(s)
      Kamio N, Hayata M, Tamura M, Tanaka H, Imai K
    • Journal Title

      FEBS Lett

      Volume: in press Issue: 11 Pages: 1604-1612

    • DOI

      10.1002/1873-3468.14084

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Butyric Acid in Saliva of Chronic Periodontitis Patients Induces Transcription of the EBV Lytic Switch Activator BZLF1: A Pilot Study.2020

    • Author(s)
      Koike R, Nodomi K, Watanabe N, Ogata Y, Takeichi O, Takei M, Kaneko T, Tonogi M, Kotani AI, Imai K
    • Journal Title

      in Vivo

      Volume: 34 Issue: 2 Pages: 587-594

    • DOI

      10.21873/invivo.11811

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epstein-Barr virus reactivation by persistent apical periodontal pathogens2020

    • Author(s)
      Himi K, Takeichi O, Imai K, Hatori K, Tamura T, Ogiso B
    • Journal Title

      Int Endod J

      Volume: 53 Pages: 492-505

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Structural insights into the potential changes in receptor binding site found in the 1998-2018 influenza B/Yamagata hemagglutinin: A putative correlation between receptor binding site structural variability and seasonal infection.2020

    • Author(s)
      1.Cueno ME, Iguchi K, , Suemitsu K, Hirano M, Hanzawa K, Isoda T, Ueno M, Iguchi R, Otani A, Imai K
    • Journal Title

      J. Mol. Graph. Model

      Volume: in press

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] EBV LMP1 in gingival epithelium potentially contributes to human chronic periodontitis via inducible IL8 production2019

    • Author(s)
      Watanabe N, Nodomi K, Koike R, Kato A, Takeichi O, Kotani A, Kaneko T, Sakagami H, Takei M, Ogata Y, Sato S, Imai K
    • Journal Title

      In Vivo

      Volume: 33 Pages: 1793-1800

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The periodontopathic bacterium Fusobacterium nucleatum induced proinflammatory cytokine Ppoduction by human respiratory epithelial cell lines and in the lower respiratory organs in Mice.2019

    • Author(s)
      Hayata M, Watanabe N, Tamura M, Kamio N, Tanaka H, Nodomi K, Miya C, Nakayama E, Ueda K, Ogata Y, Imai K
    • Journal Title

      Cell Physiol Biochem

      Volume: 53 Pages: 49-61

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cynaropicrin from Cynara scolymus L. suppresses Porphyromonas gingivalis LPS-induced production of inflammatory cytokines in human gingival fibroblasts and RANKL-induced osteoclast differentiation in RAW264.7 cells.2019

    • Author(s)
      Hayata M, Watanabe N, Kamio N, Tamura M, Nodomi K, Tanaka K, Iddamalgoda A, Tsuda H, Ogata Y, Sato S, Ueda K, Imai K
    • Journal Title

      J Nat Med

      Volume: 73 Pages: 114-123

    • NAID

      40021790096

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Singlet oxygen generated by a new nonthermal atmospheric pressure air plasma device exerts a bactericidal effect on oral pathogens.2019

    • Author(s)
      Hirano Y, Hayashi M, Tamura M, Yoshino F, Yoshida A, Masubuchi M, Imai K, Ogiso B
    • Journal Title

      J Oral sci

      Volume: 61 Pages: 521-525

    • NAID

      130007751580

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] EBV-LMP1 Potentially Contributes to Chronic Periodontitis via Inducible IL-8 Production2021

    • Author(s)
      Watanabe N, Imai K, Hasuike A, Kojima T, Kawamoto K, Karahashi Y, Sato S
    • Organizer
      General Session & Exhibition of the IADR
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Proinflammatory nature of aspirated Fusobacterium nucleatum may cause pneumonia2021

    • Author(s)
      Sho Yokoe, Kenichi Imai, Tsunehiro Ezawa, Takeshi Fukuda, Shuichi Sato
    • Organizer
      General Session & Exhibition of the IADR
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Porphyromonas gingivalis gingipains potentially affects MUC5AC gene expression and protein levels in respiratory epithelial cells2021

    • Author(s)
      Norihisa Watanabe, Sho Yokoe, Marni E. Cueno, Shuichiro Maruoka, Yasuhiro Gon, Shuichi Sato, Kenichi Imai
    • Organizer
      第25回アジア太平洋呼吸器学会学術集会
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 口腔・唾液中のSARS-CoV-2.2021

    • Author(s)
      今井健一
    • Organizer
      第63回歯科基礎医学会学術大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 口腔とCOVID-19との関連 ~口腔細菌による呼吸器疾患進展の可能性~2021

    • Author(s)
      今井健一
    • Organizer
      第24回日本歯科医学会学術大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 口腔細菌のウイルス感染症促進作用 -HIV再活性化とCOVID-19に及ぼす影響を中心に―2020

    • Author(s)
      今井健一
    • Organizer
      第34回日本エイズ学会学術集会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Proinflammatory nature of aspirated periodontopathic bacteria may cause pneumonia2020

    • Author(s)
      Miya C, Suzuki R, Nodomi K, Tamura M, Kamio N, Kaneko T, Tonogi M, Imai K
    • Organizer
      98th General Session & Exhibition of the IADR. Washington
    • Related Report
      2020 Research-status Report
  • [Presentation] 口腔と下気道の炎症性疾患との関連. -F. nucleatumによる呼吸器からの炎症性サイトカイン誘導2020

    • Author(s)
      髙橋佑和, 今井健一, 飯沼利光
    • Organizer
      第31回春期日本老年歯科医学会学術大会,
    • Related Report
      2020 Research-status Report
  • [Presentation] The periodontopathic bacterium Fusobacterium nucleatum induced proinflammatory cytokine production by human respiratory epithelial cells and in the lower respiratory organs in mice2020

    • Author(s)
      Imai k, Watanabe N, Yokoe S, Sato S
    • Organizer
      第68国際歯科研究学会日本部会[JADR]総会・学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] 下気道の炎症性疾患と口腔との関連  -歯周病原菌による呼吸器上皮細胞とマウス下気道からの炎症性サイトカイン誘導-.2020

    • Author(s)
      今井健一
    • Organizer
      第60回日本呼吸器学会学術講演会
    • Related Report
      2020 Research-status Report
  • [Presentation] 口腔フローラと健康寿命 -「細菌-ウイルス-宿主相互作用」の観点から-.2019

    • Author(s)
      今井健一
    • Organizer
      第40回日本歯内療法学会学術大会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 口腔細菌と呼吸器感染症関連微生物との相互作用 ─歯周病原細菌が肺炎とインフルエンザの発症に及ぼす影響─.2019

    • Author(s)
      神尾宜昌, 田村宗明, 今井健一
    • Organizer
      第93回日本感染症学会総会・学術講演会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] EBV関連悪性リンパ腫モデルマウスの作製とヒトリンパ腫との組織レベルでの比較検討2019

    • Author(s)
      小池亮, 今井健一
    • Organizer
      第61回歯科基礎医学会学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] P. gingivalis LPS誘導性炎症性サイトカイン産生とRANKL誘導性破骨細胞分化に対するアーティチョーク由来シナロピクリンの抑制効果2019

    • Author(s)
      渡辺典久, 横江将, 佐藤秀一, 今井健一
    • Organizer
      第61回歯科基礎医学会学術大会
    • Related Report
      2019 Research-status Report
  • [Book] 口腔微生物学 感染と免疫2021

    • Author(s)
      石原和幸、今井健一、大島朋子、落合智子、葛城啓彰、清浦有祐、高橋幸裕、田中芳彦、浜田信城、
    • Total Pages
      423
    • Publisher
      学建書院
    • Related Report
      2020 Research-status Report
  • [Remarks] 日本大学歯学部感染症免疫学講座

    • URL

      http://www2.dent.nihon-u.ac.jp/microbiology/

    • Related Report
      2021 Annual Research Report
  • [Remarks] 日本大学歯学部細菌学

    • URL

      http://www2.dent.nihon-u.ac.jp/microbiology/

    • Related Report
      2020 Research-status Report

URL: 

Published: 2019-04-18   Modified: 2023-01-30  

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