The study of oral streptococcal pathogenicity of autoimmune hepatitis

• Project/Area Number: 21592387
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: The University of Tokushima
• Principal Investigator: HIROTA Kastuhiko 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 准教授 (60199130)
• Co-Investigator(Kenkyū-buntansha): MIYAKE Youichirou 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 教授 (80136093) ; NEMOTO Ken 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 助教 (10218274) ; KAYAMA Shizuo 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 助教 (50432761)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: S. intermedius / 細胞溶解毒素 / 胆管上皮細胞 / アポトーシス / Ca^<2+>振動 / NFAT / サイトカイン / カルシニューリン / 感染防御免疫 / サイトカインバランス / Bio-plex測定法 / THP-1 / バランス異常 / IL-10 / S.intermedius / 自己免疫性肝疾患 / 細菌毒素 / 小胞体異常 / gp210 / BiP / ヌクレアポリン / 口腔レンサ球菌

Research Abstract

In the present study we analyzed possible relationship between calcium oscillations and each phenomenon in order to find out the molecular mechanisms in ILY-induced bile duct epithelial cells. Intracellular free calcium was analyzed by performing calcium imaging analysis of Fura-2 loaded cells. Increased free calcium was initially detected in the nuclei of ILY-treated cells subsequently followed with markedly increase in ER area. Calcineurin inhibitor cyclosporine A prevented ILY-induced calcineurin/ NFAT1 activation, cell death, and calcium oscillations. ILY in concentration of 10-40 ng/ ml capable of inducing calcium oscillations, activation of calcineurin/ NFAT1 signalling pathway ; inactivation of PI3K/ AKT/ MTOR pathway, and caused ER stress disorder resulted non-apoptotic cell death in HuCCT1 cells.

Research Products

• [Journal Article] MPC-polymer reduces adherence and biofilm formation by oral bacteria (2011)
  • Author(s): Hirota K, Yumoto H, Miyamoto K, Yamamoto N, Murakami K, Hoshino Y, Matsuo T, Miyake Y
  • Journal Title: J Dent Res Volume: 90 Issue: 7 Pages: 900-905
  • DOI: 10.1177/0022034511402996
  • Peer Reviewed
• [Journal Article] Intermedilysin induces EGR-1 expression through calcineurin/ NFAT pathway in human cholangiocellular carcinoma cells (2011)
  • Author(s): Susilowati H, Okamura H, Hirota K, Shono M, Yoshida K, Murakami K, Tabata A, Nagamune H, Haneji T, Miyake Y
  • Journal Title: Biochem Biophys Res Commun Volume: 404(1) Issue: 1 Pages: 57-61
  • DOI: 10.1016/j.bbrc.2010.11.057
  • Peer Reviewed
• [Journal Article] Intermedilysin induces EDR-1 expression through calcineurin/NFAT pathway in human cholangiocellular carcinoma cells (2011)
  • Author(s): Heni Susilowati, et al
  • Journal Title: Biochemical and Biophysical Research communications Volume: 404 Pages: 57-61
  • Peer Reviewed
• [Journal Article] High prevalence of Pseudomonas aeruginosa from oropharyngeal biofilm in patients with cerebrovascular infarction and dysphagia (2010)
  • Author(s): Hirota K, Yoneyama T, Sakamoto M, Miyamoto H, Kurihara M, Kayama S, Murakami K, Yumoto H, Matsuo T, Miyake Y
  • Journal Title: Chest Volume: 38 Issue: 1 Pages: 237-238
  • DOI: 10.1378/chest.10-0240
  • Peer Reviewed
• [Journal Article] Long-term bacterial exposure can trigger nonsuppurative destructive cholangitis associated with multifocal epithelial inflammation (2010)
  • Author(s): Haruta I, Kikuchi K, Hashimoto E, Nakamura M, Miyakawa H, Hirota K, Shibata N, Kato H, Arimura Y, Kato Y, Uchiyama T, Nagamune H, Kobayashi M, Miyake Y, Shiratori K, Yagi J
  • Journal Title: Lab Invest Volume: 90 Pages: 577-588
  • Peer Reviewed
• [Journal Article] Long-term bacterial exposure can trigger nonsuppurative destructive cholangitis associated with multifocal epithelial inflammation. (2010)
  • Author(s): Haruta I.
  • Journal Title: Lab Invest Volume: 90 Pages: 577-588
  • Peer Reviewed
• [Journal Article] High prevalence of Pseudomonas aeruginosa from oropharyngeal biofilm in patients with cerebrovascular infarction and dysphagia. (2010)
  • Author(s): Hirota K.
  • Journal Title: Chest Volume: 138 Pages: 237-238
  • Peer Reviewed
• [Journal Article] Long-term bacterial exposure can trigger nonsuppurative destructive cholangitis associated with multifocal epithelial inflammation (2010)
  • Author(s): Ikuko Haruta
  • Journal Title: Laboratory Investigation (印刷中)
  • Peer Reviewed
• [Journal Article] High incidence of Pseudomonas aeruginosa from oropharyngeal biofilm in cerebrovascular infarction patients with dysphagia (2010)
  • Author(s): Katsuhiko Hirota
  • Journal Title: CHEST (印刷中)
  • Peer Reviewed
• [Presentation] The effect of extracellular DNA on the development of Streptococcus intermedius biofilm (2011)
  • Author(s): Asikin Nur, et al
  • Organizer: 第64回日本細菌学会中国・四国支部総会
  • Place of Presentation: 岡山大学津島キャンパス(岡山)
  • Year and Date: 2011-10-22
• [Presentation] Gene expression profiling of human monocytic THP-1 cells stimulated with extracellular Streptococcus intermedius histine-like DNA binding (2011)
  • Author(s): Hirota K, et al
  • Organizer: International Union of microbiological Science 2011 Congrecc
  • Place of Presentation: Sapporo Convention Center (Hokkaido)
  • Year and Date: 2011-09-07
• [Presentation] The effect of extracellular DNA on the development of Streptococcus intermedius biofilm (2011)
  • Author(s): Asikin Nur, Katsuhiko Hirota, Hiromichi Yumoto, Kouji Hirao, Kanako Takahashi, Keiji Murakami, Yoichiro Miyake
  • Organizer: 第64回日本細菌学会中国・四国支部総会
  • Place of Presentation: 岡山大学津島キャンパス(岡山市)
• [Presentation] Gene expression profiling of human monocytic THP-1 cells stimulated with extracellular Streptococcus intermedius histone-like DNA binding protein (2011)
  • Author(s): Katsuhiko Hirota, Hiromichi Yumoto, Asikin Nur, Kouji Hirao, Kanako Takahashi, Dali Liu, Keiji Murakami, Takashi Matsuo, Yoichiro Miyake
  • Organizer: International Union of Microbiological Societies 2011 Congress
  • Place of Presentation: Sapporo Convention Center,(Hokkaido, Japan)
• [Presentation] THP-1細胞のケモカイン産生に及ぼす口腔レンサ球菌ヒストン様DNA結合タンパク質の影響 (2010)
  • Author(s): 近藤洋史, 小野恒子, 弘田克彦, 村上圭史, 三宅洋一郎, 湯本浩通, 高橋加奈子, 平尾功治, 松尾敬志
  • Organizer: 第34回徳島県医学検査学会
  • Place of Presentation: 徳島大学医学部保健学科C棟(徳島市)
  • Year and Date: 2010-12-12
• [Presentation] Intermedilysin による小胞体異常の分子機構の解明 (2010)
  • Author(s): 弘田克彦
  • Organizer: 第83回日本細菌学会総会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2010-03-28
• [Presentation] Streptococcus intermedius由来histone様DNA結合タンパク質がヒト単球系細胞のサイトカイン・ケモカイン産生に及ぼす影響 (2010)
  • Author(s): 平尾功治, 湯本浩通, 弘田克彦, 高橋加奈子, 木村智子, 三宅洋一郎
  • Organizer: 第63回日本細菌学会中国・四国支部総会
  • Place of Presentation: 松山大学文京キャンパス(松山市)
• [Presentation] Streptococcus intermediusヒストン様タンパク質がTHP-1細胞のサイトカインバランスに及ぼす影響 (2010)
  • Author(s): 弘田克彦, 三宅洋一郎
  • Organizer: 第52回歯科基礎医学会学術大会・総会
  • Place of Presentation: タワーホール船堀(東京都)
• [Presentation] Intermedilysinによる小胞体異常の分子機構の解明 (2010)
  • Author(s): 弘田克彦, 鹿山鎭男, 村上圭史, 湯本浩通, 三宅洋一郎
  • Organizer: 第83回日本細菌学会総会
  • Place of Presentation: パシフィコ横浜(横浜市)
• [Presentation] Streptococcus intermedius由来histone様DNA結合タンパク質がヒト単球系細胞のサイトカイン・ケモカイン産生に及ぼす影響 (2010)
  • Author(s): 平尾功治
  • Organizer: 第63回日本細菌学会中国・四国支部総会
  • Place of Presentation: 松山大学
• [Presentation] Intermedilysin に誘導されるHuCCT1細胞gp210の分布変動 (2009)
  • Author(s): 弘田克彦
  • Organizer: 第62回日本細菌学会中国・四国支部総会
  • Place of Presentation: 広島大学霞キャンパス広仁会館(新潟県)
  • Year and Date: 2009-10-17
• [Presentation] 誘電泳動インピーダンス計測法を用いた迅速微生物数測定装置による口腔微生物の測定評価 (2009)
  • Author(s): 弘田克彦
  • Organizer: 第51回歯科基礎医学会学術大会・総会
  • Place of Presentation: 朱鷺メッセ 新潟コンベンションセンター(新潟県)
  • Year and Date: 2009-09-09
• [Presentation] Intermedilysinに誘導されるHuCCT1細胞gp210の分布変動 (2009)
  • Author(s): 弘田克彦, 鹿山鎭男, 湯本浩通, 三宅洋一郎
  • Organizer: 第62回日本細菌学会中国・四国支部総会
  • Place of Presentation: 広島大学霞キャンパス(広島市)
• [Remarks]
  • URL: http://www.dent.tokushima-u.ac.jp/saikin/research_J.html
• [Remarks]
  • URL: http://www.dent.tokushima-u.ac.jp/saikin/staff_J.html