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Strategic approach towards etiological elucidation and novel therapy development of periodontitis attributed to EBV

Research Project

Project/Area Number 16K11526
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pathobiological dentistry/Dental radiology
Research InstitutionNihon University

Principal Investigator

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

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords歯周病 / 歯周疾患 / EBウイルス / 炎症 / 根尖性歯周炎 / 炎症性サイトカイン / インプラント周囲炎 / EBV / EBV / 炎症性サイトカイン」 / NOGマウス
Outline of Final Research Achievements

Human chronic periodontitis is a major public health problem, the major etiology of which has recently been revealed to be neutrophil infiltration into the periodontium. It affects over half of the adult population worldwide. 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 concentrations of IL-8 were produced due to LMP1 in time- and dose-dependent manners in human gingival cells. In addition, P. endodontalis induces the EBVs lytic switch transactivator ZEBRA by histone modification. 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

超高齢社会を迎えるわが国では、歯周疾患の罹患率の上昇と重症度のより高い患者の増加が見込まれる。病気の進行は歯の喪失に繋がるため、食生活の著しい低下を招く。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が関与するがんや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)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (25 results)

All 2018 2017 2016

All Journal Article (10 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Open Access: 3 results) Presentation (14 results) (of which Int'l Joint Research: 3 results,  Invited: 4 results) Book (1 results)

  • [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 cells2018

    • Author(s)
      Hayata Mayumi、Watanabe Norihisa、Kamio Noriaki、Tamura Muneaki、Nodomi Keiko、Tanaka Kiyotaka、Iddamalgoda Arunasiri、Tsuda Hiromasa、Ogata Yorimasa、Sato Shuichi、Ueda Kouichiro、Imai Kenichi
    • Journal Title

      Journal of Natural Medicines

      Volume: 73 Issue: 1 Pages: 114-123

    • DOI

      10.1007/s11418-018-1250-6

    • NAID

      40021790096

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Porphyromonas endodontalis reactivates latent Epstein-Barr virus.2018

    • Author(s)
      Makino K, Takeichi O, Imai K, Inoue H, Hatori K, Himi K, Saito I, Ochiai K, Ogiso B
    • Journal Title

      International Endodontic Journal

      Volume: 51 Issue: 12 Pages: 1410-1419

    • DOI

      10.1111/iej.12959

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Various cellular components change as the rat ages: An insight into the putative overall age-related cellular stress network2018

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

      Experimental Gerontology

      Volume: 102 Pages: 36-42

    • DOI

      10.1016/j.exger.2017.11.021

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] MiR-200b attenuates IL-6 production through IKKβ and ZEB1 in human gingival fibroblasts.2018

    • Author(s)
      Matsui S, Zhou L, Nakayama Y, Mezawa M, Kato A, Suzuki N, Tanabe N, Nakayama T, Suzuki Y, Kamio N, Takai H, Ogata Y
    • Journal Title

      Inflamm Res

      Volume: 67 Issue: 11-12 Pages: 965-973

    • DOI

      10.1007/s00011-018-1192-1

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Network analytics approach towards identifying potential antivirulence drug targets within the Staphylococcus aureus staphyloxanthin biosynthetic network2018

    • Author(s)
      Marni E. Cueno, Kenichi Imai
    • Journal Title

      Archives of Biochemistry and Biophysics

      Volume: 645 Pages: 81-86

    • DOI

      10.1016/j.abb.2018.03.010

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 歯周病の病因に関する最近の話題 -細菌とウイルスの相互作用-.2018

    • Author(s)
      1.今井健一
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 69 Pages: 180-185

    • NAID

      40021473960

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Prevalence of Epstein-Barr virus DNA and Porphyromonas gingivalis in Japanese peri-implantitis patients.2017

    • Author(s)
      Kato A, Imai K, Sato H, Ogata Y
    • Journal Title

      BMC Oral Health

      Volume: 17(1) Issue: 1 Pages: 148-148

    • DOI

      10.1186/s12903-017-0438-6

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Periodontal disease level-butyric acid putatively contributes to the ageing blood: A proposed link between periodontal diseases and the ageing process.2017

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

      Mech Ageing

      Volume: 162 Pages: 100-105

    • DOI

      10.1016/j.mad.2017.01.005

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Bactericidal effect of hydroxyl radicals generated by the sonolysis and photolysis of hydrogen peroxide for endodontic applications2017

    • Author(s)
      Ibi H, Hayashi M, Yoshino F, Tamura M, Yoshida A, Kobayashi Y, Shimizu K, Lee M-C, Imai K, Ogiso B
    • Journal Title

      Microbial Pathogenesis

      Volume: 103 Pages: 65-70

    • DOI

      10.1016/j.micpath.2016.12.010

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 歯周病の発症と進行へのウイルス感染の関与の可能性2016

    • Author(s)
      小方頼昌, 加藤彩子, 今井健一, 落合邦康
    • Journal Title

      千葉県歯科医学会誌

      Volume: 6 Pages: 8-11

    • Related Report
      2016 Research-status Report
  • [Presentation] 口腔の特性と常在微生物叢による感染症2018

    • Author(s)
      今井健一
    • Organizer
      第33回日本環境感染学会総会・学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 口腔衛生状態と呼吸器疾患との関連から医療連携を再考する2018

    • Author(s)
      今井健一
    • Organizer
      第27回日本有病者歯科医療学会総会・学術大会 第38回日本歯科薬物療法学会学術大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 口腔細菌と全身疾患との関わり2018

    • Author(s)
      今井健一
    • Organizer
      平成30年度日本補綴歯科学会東京支部学術大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] EBV-LMP1 induces IL-8 production via regulation of the NF-kB pathway in the human gingival epithelial cells2018

    • Author(s)
      Kenichi Imai
    • Organizer
      The 43rd FEBS Congress
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] EBV reactivation by refractory apical periodontitis-related bacteria2018

    • Author(s)
      K. Himi, O.Takeichi, K. Hatori, K. Makino, H. Kudo, H. Tanaka, K. Imai, B. Ogiso
    • Organizer
      IADR
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] EBV-LMP1 promotes production of inflammatory cytokines through NF-kB signaling in gingival epithelial cells: its potentioal implication in periodontitis progression.2017

    • Author(s)
      今井健一
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 口腔細菌による誤嚥性肺炎発症メカニズムの解明;歯周病原菌は種々の呼吸器系上皮細胞からの炎症性サイトカイン産生を誘導する2017

    • Author(s)
      渡辺典久, 早田真由美, 田村宗明, 神尾宜昌, 田中 一, 佐藤秀一, 今井健一
    • Organizer
      日本歯周病学会60周年記念京都大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 口腔細菌による誤嚥性肺炎発症機序の解明2: 歯周病原菌は呼吸器上皮細胞の炎症性サイトカイン産生を誘導する.2017

    • Author(s)
      今井健一, 早田真由美, 渡辺典久, 神尾宜昌, 田村宗明, 田中 一, 植田耕一郎
    • Organizer
      第23回日本摂食嚥下リハビリテーション学会学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 歯周病の発生と進展におけるEBV関与の可能性-EBVのLMP1はNF-κBを活性化し歯肉上皮細胞からの炎症性サイトカインを誘導する-2017

    • Author(s)
      今井健一, 渡邊典久, 佐藤秀一, 小方頼昌
    • Organizer
      第60回春季日本歯周病学会学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] EBVによる歯周病の発症・進展機序の解明 - EBVのLMP1はNF-κBを活性化し歯肉上皮細胞からのIL-8産生を誘導する-2017

    • Author(s)
      渡辺典久, 小池 亮, 早田真由美, 金子忠良, 佐藤秀一, 今井健一
    • Organizer
      第59回歯科基礎医学会学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 慢性歯周炎の発症と進行へのエプスタインバーウイルス(EBV)と P. gingivalisの関与2016

    • Author(s)
      加藤彩子 今井健一 神尾宜昌 岡林堅 小方頼昌
    • Organizer
      第23回 日本歯科医学会総会
    • Place of Presentation
      福岡国際会議場(福岡県福岡市)
    • Year and Date
      2016-10-21
    • Related Report
      2016 Research-status Report
  • [Presentation] ィンプラント周囲滲出液からのエプスタインバーウイルス(EBV)DNAの検出2016

    • Author(s)
      小方頼昌 今井健一 神尾宜昌 高井英樹 加藤 彩子
    • Organizer
      第23回 日本歯科医学会総会
    • Place of Presentation
      福岡国際会議場(福岡県福岡市)
    • Year and Date
      2016-10-21
    • Related Report
      2016 Research-status Report
  • [Presentation] 口腔細菌のウィルス感染症促進作用ーEBVおよびインフルエンザ感染に及ぼす影響-2016

    • Author(s)
      今井健一, 神尾宜昌
    • Organizer
      第19回日本臨床腸内微生物学会総会学術大会
    • Place of Presentation
      杏林大学(東京都三鷹市)
    • Year and Date
      2016-08-27
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Quantitative Analysis of EBV DNA and P. gingivalis Associated with Peri-implantitis2016

    • Author(s)
      Ayako Kato, Kenichi Imai, Kuniyasu Ochiai, and Yorimasa Ogata
    • Organizer
      IADR General Session
    • Place of Presentation
      Seoul(Korea)
    • Year and Date
      2016-06-22
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Book] 口腔微生物学 -感染と免疫- 第6版2018

    • Author(s)
      石原和幸 今井健一 小川知彦 落合邦康 落合智子 葛城啓彰 上西秀則 清浦有祐 古西清 田中芳彦 中澤太 浜田信城 前田伸子
    • Total Pages
      433
    • Publisher
      学研書院
    • Related Report
      2018 Annual Research Report

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Published: 2016-04-21   Modified: 2021-12-27  

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