Study of autoimmune reaction induced by Epstein-Brr virus (EBV)-encoded small RNA (EBER)

• Project/Area Number: 24592783
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Morphological basic dentistry
• Research Institution: Nihon Pharmaceutical University (2013-2014); Tsurumi University (2012)
• Principal Investigator: INOUE HIROKO 日本薬科大学, 薬学部, 准教授 (50367306)
• Co-Investigator(Kenkyū-buntansha): SAITO Ichiro 鶴見大学, 歯学部, 教授 (60147634) ; MURAMATSU Takashi 東京歯科大学, 歯学部, 教授 (00276982) ; RYO Kofuchi 鶴見大学, 歯学部, 講師 (10298268)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: Epstein-Barr virus / シェーグレン症候群 / 自己抗体 / TLR / EBウイルス / EBER / SSB/La

Outline of Final Research Achievements

Sjogren's syndrome (SS) is an organ-specific autoimmune disease caused by the progressive loss of exocrine glands and is associated with several autoimmune phenomena. Several reports have suggested that reactivation of Epstein-Barr virus (EBV) may be a cause of SS. In this study, we revealed that EBV noncoding RNA, EBER, induced various cytokine in human salivary gland epithelial cell lines. In C57/B6 mice, nuclear extract (NE) from EBV infected B cell line induced expression of autoantibody, anti-SSB/La. Moreover, in NZW/NZB F1 mice, recombinant EBER induced anti-SSB/La antibody more efficiently than poly(I:C), TLR ligand.

Research Products

• [Journal Article] Evaluation of the effects of quercetin on damaged salivary secretion (2015)
  • Author(s): Takahashi, A. Inoue, H. Mishima, K. Ide, F. Nakayama, R. Hasaka, A. Ryo, K. Ito, Y. Sakurai, T. Hasegawa, Y. Saito, I.
  • Journal Title: PLoS One Volume: 10 Issue: 1 Pages: e0116008-e0116008
  • DOI: 10.1371/journal.pone.0116008
  • Peer Reviewed / Open Access
• [Journal Article] Role of the histone H3 lysine 9 methyltransferase Suv39 h1 in maintaining Epsteinn-Barr virus latency in B95-8 cells. (2014)
  • Author(s): Imai K, Kamio N, Cueno ME, Saito Y, Inoue H, Saito I, Ochiai K.
  • Journal Title: The FEBS journal Volume: 281 Issue: 9 Pages: 2148-2158
  • DOI: 10.1111/febs.12768
  • Peer Reviewed / Open Access
• [Journal Article] Therapeutic effects of isoflavones on impaired salivary secretion (2014)
  • Author(s): Ryo, K. Takahashi, A. Tamaki, Y. Ohnishi-Kameyama, M. Inoue, H. Saito, I.
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 55 Issue: 3 Pages: 168-173
  • DOI: 10.3164/jcbn.14-49
  • NAID: 130004694543
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed / Open Access
• [Journal Article] Primary and secondary surveys on epidemiology of Sjogren's syndrome in Japan (2014)
  • Author(s): Tsuboi, H. Asashima, H. Takai, C. Hagiwara, S. Hagiya, C. Yokosawa, M. Hirota, T. Umehara, H. Kawakami, A. Nakamura, H. Sano, H. Tsubota, K. Ogawa, Y. Takamura, E. Saito, I. Inoue, H. Nakamura, S. Moriyama, M. Takeuchi, T. Tanaka, Y. Hirata, S. Mimori, T. Yoshifuji, H. Ohta, A. Matsumoto, I. Sumida, T.
  • Journal Title: Mod Rheumatol Volume: 24 Issue: 3 Pages: 464-70
  • DOI: 10.3109/14397595.2013.843765
  • Peer Reviewed / Open Access
• [Journal Article] Validation of different sets of criteria for the diagnosis of Sjögren's syndrome in Japanese patients. (2013)
  • Author(s): Tsuboi H
  • Journal Title: Mod Rheumatol. Volume: 23 Issue: 2 Pages: 219-225
  • DOI: 10.1007/s10165-012-0812-9
  • Peer Reviewed
• [Journal Article] Treatment of salivary gland hypofunction by transplantation with dental pulp cells. (2013)
  • Author(s): Yamamura Y, Yamada H, Sakurai T, Ide F, Inoue H, Muramatsu T, Mishima K, Hamada Y, Saito I.
  • Journal Title: Arch Oral Biol Volume: 58 Issue: 8 Pages: 935-942
  • DOI: 10.1016/j.archoralbio.2013.02.015
  • Peer Reviewed
• [Journal Article] Aryl Hydrocarbon Receptor-Mediated Induction of EBV Reactivation as a Risk Factor for Sjogren's Syndrome (2012)
  • Author(s): Hiroko Inoue
  • Journal Title: J Immunol Volume: 188 Issue: 9 Pages: 4654-4662
  • DOI: 10.4049/jimmunol.1101575
  • Peer Reviewed
• [Journal Article] Transplantation of side population cells restores the function of damaged exocrine glands through clusterin (2012)
  • Author(s): Mishima K., Inoue H., Nishiyama T., Mabuchi Y., Amano Y., Ide F., Matsui M., Yamada H., Yamamoto G., Tanaka J., Yasuhara R., Sakurai T., Lee M., Chiba K., Sumimoto H., Kawakami Y., Matsuzaki Y., Tsubota K., Saito I
  • Journal Title: Stem Cells Volume: 30 Issue: 9 Pages: 1925-37
  • DOI: 10.1002/stem.1173
  • Peer Reviewed
• [Journal Article] The periodontal pathogen Porphyromonas gingivalis induces the Epstein-Barr virus lytic switch transactivator ZEBRA by histone modification (2012)
  • Author(s): Kenichi Imai
  • Journal Title: Biochimie Volume: 94 Issue: 3 Pages: 839-846
  • DOI: 10.1016/j.biochi.2011.12.001
  • Peer Reviewed
• [Presentation] EBVの再活性化とシェーグレン症候群 (2014)
  • Author(s): 井上裕子
  • Organizer: 第23回日本シェーグレン症候群学会学術集会
  • Place of Presentation: ホテルニュー長崎
  • Year and Date: 2014-09-12 – 2014-09-13
• [Presentation] 唾液分泌障害に対するケルセチンの効果の検討 (2014)
  • Author(s): 高橋絢子、中山亮子、葉阪彩加、伊藤由美、梁 洪淵、櫻井 孝、栗原 毅、井出文雄、美島健二、井上裕子、斎藤一郎
  • Organizer: 第14回抗加齢医学会総会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2014-06-06 – 2014-06-08
• [Presentation] 分泌機能促進因子の検討 (2014)
  • Author(s): 井上裕子
  • Organizer: 第14回抗加齢医学会総会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2014-06-06 – 2014-06-08
• [Presentation] 液分泌障害に対するケルセチンの効果の検討 (2014)
  • Author(s): 高橋絢子、井上裕子、美島健二、伊藤由美、梁 洪淵、櫻井 孝、井出文雄、斎藤一郎
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島国際会議場
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] The molecular mechanism of salivary dysfunction amelioration by calorie restriction (2014)
  • Author(s): Hiroko Inoue1,2, Kenji Mishima3, Takahiko Shimizu4, Motoko Kawashima5, Ayaka Hasaka1, Kazuo Tsubota5, Ichiro Saito1
  • Organizer: Biennial Meeting of Society for Free Radical Research International
  • Place of Presentation: 京都国際会議場
• [Presentation] Aryl Hydrocarbon Receptor-Mediated Induction of Epstein-Barr Virus Reactivation as a Risk Factor for Sjogren’s Syndrome (2013)
  • Author(s): Hiroko Inoue, Ichiro Saito
  • Organizer: International Sjogren's syndrome meeting
  • Place of Presentation: Kyoto Hotel Okura
  • Invited
• [Presentation] 長期フェニレフリン刺激によるカリクレイン分泌抑制とPKC活性化の関与 (2013)
  • Author(s): 吉野陽子、今村武浩、山近重生、井上裕子、斎藤一郎、前田伸子、中川洋一
  • Organizer: 第67回日本口腔科学会
  • Place of Presentation: 栃木県総合文化センター
• [Presentation] ドライマウス（口腔乾燥症）に対するイソフラボンの唾液分泌促進効果の検討 (2013)
  • Author(s): 梁 洪淵、井上裕子、亀山眞由美、新美 愛、高橋絢子、伊藤由美、村松敬、玉置洋、斎藤一郎
  • Organizer: 日本抗加齢医学会
  • Place of Presentation: パシフィコ横浜会議センター
• [Presentation] ケルセチンによる唾液分泌機能亢進の可能性の検討 (2013)
  • Author(s): 高橋絢子、井上裕子、梁 洪淵、伊藤由美、村松敬、斎藤一郎
  • Organizer: 日本抗加齢医学会
  • Place of Presentation: パシフィコ横浜会議センター
• [Presentation] カロリー制限による唾液分泌能改善効果の分子機構の解明 (2013)
  • Author(s): 井上裕子、美島健二、清水孝彦、村松敬、伊藤由美、梁洪淵、井出文雄、川島素子、坪田一男、斎藤一郎
  • Organizer: 日本抗加齢医学会
  • Place of Presentation: パシフィコ横浜会議センター
• [Presentation] カロリー制限による唾液分泌能改善効果の分子機構の解明 (2013)
  • Author(s): 井上裕子、美島健二、清水孝彦、村松敬、伊藤由美、梁洪淵、井出文雄、斎藤一郎
  • Organizer: 日本病理学会
  • Place of Presentation: ロイトン札幌
• [Presentation] シェーグレン症候群におけるary hydrocarbon受容体を介したEBウイルス再活性化機構の解明 (2012)
  • Author(s): 井上裕子
  • Organizer: 日本シェーグレン症候群学会
  • Place of Presentation: ウェスティン都ホテル京都（京都府）
  • Invited
• [Presentation] イソフラボンによる唾液分泌促進効果の検討 (2012)
  • Author(s): 新美愛、高橋絢子、梁洪淵、井上裕子、斎藤一郎
  • Organizer: 日本口腔検査学会
  • Place of Presentation: 日本大学法学部（東京都）
• [Presentation] 唾液分泌改善を目的とした歯髄細胞から血管内皮細胞への分化誘導の検討 (2012)
  • Author(s): 山村優花、山田浩之、濱田良樹、井上裕子、村松敬、美島健二、斎藤一郎
  • Organizer: 日本抗加齢医学会
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Presentation] カロリー制限による唾液分泌改善効果の分子機構の解明 (2012)
  • Author(s): 井上裕子、美島健二、川島素子、坪田一男、斎藤一郎
  • Organizer: 日本唾液腺学会
  • Place of Presentation: 文京学院大学（東京都）
• [Presentation] The molecular mechanism of salivary dysfunction amelioration by calorie restriction (2012)
  • Author(s): 井上裕子、美島健二、清水孝彦、川島素子、坪田一男、斎藤一郎
  • Organizer: 日本分子生物学会
  • Place of Presentation: マリンメッセ福岡（福岡県）