A strategic approach to elucidate the etiology of EBV-induced periodontitis and to develop novel therapies
| Project/Area Number |
19K10078
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 57020:Oral pathobiological science-related
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| Research Institution | Nihon University |
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Principal Investigator |
IMAI Kenichi 日本大学, 歯学部, 教授 (60381810)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| 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)
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| Keywords | EB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 |
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| 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。
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| 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.
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| 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。
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Report
(4 results)
Research Products
(35 results)
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[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
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Journal Title
Int J Mol Sci.
Volume: 23(2)
Issue: 2
Pages: 80-80
DOI
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
Front Medicine
Volume: 8
Pages: 613412-613412
DOI
Related Report
Peer Reviewed / Open Access
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[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
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Journal Title
J. Mol. Graph. Model
Volume: in press
Related Report
Peer Reviewed / Open Access
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[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
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Journal Title
In Vivo
Volume: 33
Pages: 1793-1800
Related Report
Peer Reviewed / Open Access
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[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
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Journal Title
Cell Physiol Biochem
Volume: 53
Pages: 49-61
Related Report
Peer Reviewed / Open Access
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[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
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Journal Title
J Nat Med
Volume: 73
Pages: 114-123
NAID
Related Report
Peer Reviewed / Open Access
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