Basic study on the regulation of inflammation of periodontal tissue by targeting Toll-like receptor 4

• Project/Area Number: 24593126
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Periodontal dentistry
• Research Institution: Nagasaki University
• Principal Investigator: YOSHIMURA Atsutoshi 長崎大学, 医歯薬学総合研究科(歯学系), 准教授 (70253680)
• Co-Investigator(Kenkyū-buntansha): KANEKO Takashi 福岡歯科大学, 口腔医療センター, 教授 (10284697) ; HARA Yoshitaka 長崎大学, 大学院医歯薬学総合研究科(歯学系), 教授 (60159100)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 歯周炎 / 歯肉縁下プラーク / 歯肉縁上プラーク / Toll-like receptor 4 / Toll-like receptor 2 / 炎症性サイトカイン / 歯周病 / 遺伝子多型 / Toll-like receptor / 歯肉炎指数 / 年齢 / 性別 / グラム陰性菌 / LPS

Outline of Final Research Achievements

Bacterial components in dental plaque activate innate immune system via receptors, such as Toll-like receptors (TLRs). To control the inflammatory responses in periodontal tissue, we analyzed TLR2- and TLR4-stimulating ability of supra- and subgingival plaque. We found that proinflammatory cytokine production by peripheral blood mononuclear leukocytes is mainly mediated by TLR4.
Controlling TLR4-stiulating ability of supra- and subgingival plaque might be useful for preventing the progression of periodontal diseases.

Research Products

• [Int'l Joint Research] ボン大学(ドイツ)
• [Journal Article] Salivary pathogen and serum antibody to assess the progression of chronic periodontitis: a 24-mo prospective multicenter cohort study (2016)
  • Author(s): Morozumi T, Nakagawa T, Nomura Y, Sugaya T, Kawanami M, Suzuki F, Takahashi K, Abe Y, Sato S, Makino-Oi A, Saito A, Takano S, Minabe M, Nakayama Y, Ogata Y, Kobayashi H, Izumi Y, Sugano N, …., Yoshimura A, Hara Y, ….
  • Journal Title: Journal of Periodontal Research Volume: 印刷中 Issue: 6 Pages: 768-778
  • DOI: 10.1111/jre.12353
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Analysis of the ability of subgingival plaque to stimulate Toll-like receptor (TLR)2 and TLR4 (2016)
  • Author(s): Ziauddin SM, Montenegro RJL, Sato K, Yoshioka H, Ozaki Y, Kaneko T, Yoshimura A, Hara Y
  • Journal Title: Journal of Periodontology Volume: 印刷中
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The histopathological comparison on the destruction of the periodontal tissue between normal junctional epithelium and long junctional epithelium (2016)
  • Author(s): Noguchi S, Ukai T, Kuramoto A, Yoshinaga Y, Nakamura H, Takamori Y, Yamashita Y, Hara Y
  • Journal Title: Journal of Periodontal Research Volume: 印刷中 Issue: 1 Pages: 74-82
  • DOI: 10.1111/jre.12370
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Histopathological comparison of the onset of peri-implantitis and periodontitis in rats (2016)
  • Author(s): Takamori Y, Atsuta I, Nakamura H, Sawase T, Koyano K, Hara Y
  • Journal Title: Clinical Oral Implants Research Volume: 印刷中 Issue: 2 Pages: 163-170
  • DOI: 10.1111/clr.12777
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 37.RANKL pretreatment plays an important role in the differentiation of pit-forming osteoclasts induced by TNF-α on murine bone marrow macrophages. (2015)
  • Author(s): Yamashita Y, Ukai T, Nakamura H, Yoshinaga Y, Kobayashi H, Takamori Y, Noguchi S, Yoshimura A, Hara Y
  • Journal Title: Arch Oral Biol. Volume: 60(9) Issue: 9 Pages: 1273-1282
  • DOI: 10.1016/j.archoralbio.2015.06.002
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] T Cells Are Not Crucial in Bone Resorption in Response to Traumatic Occlusion (2015)
  • Author(s): 中村弘隆, 鵜飼 孝, 吉永泰周, 白石千秋, 吉永美穂, 吉村篤利, 原 宜興
  • Journal Title: The Japanese Journal of Conservative Dentistry Volume: 58 Issue: 1 Pages: 35-41
  • DOI: 10.11471/shikahozon.58.35
  • NAID: 130005005974
  • ISSN: 0387-2343, 2188-0808
  • Peer Reviewed / Open Access
• [Journal Article] The Effect of Gram-positive or -negative Bacteria Homogenates on Periodontal Tissue of Immunized Rats (2014)
  • Author(s): 吉永泰周，長野史子，金子高士，鵜飼孝，吉村篤利，尾崎幸生，吉永美穂，白石千秋，中村弘隆，藏本明子，高森雄三，野口惠司，山下恭德，泉聡史，原宜興
  • Journal Title: The Japanese Journal of Conservative Dentistry Volume: 57 Issue: 2 Pages: 154-161
  • DOI: 10.11471/shikahozon.57.154
  • NAID: 130004669776
  • ISSN: 0387-2343, 2188-0808
  • Peer Reviewed / Open Access
• [Journal Article] ROCK inhibitor Y-27632 maintains the proliferation of confluent human messenchymal stem cells. (2014)
  • Author(s): Nakamura K, Yoshimura A, Kaneko T, Sato K, Hara Y.
  • Journal Title: J Periodontal Res Volume: 49 Issue: 3 Pages: 363-370
  • DOI: 10.1111/jre.12114
  • Peer Reviewed
• [Journal Article] Nakatsu S, Yoshinaga Y, Kuramoto A, Nagano F, Ichimura I, Oshino K, Yoshimura A, Yano Y, Hara Y (2014)
  • Author(s): Nakatsu S, Yoshinaga Y, Kuramoto A, Nagano F, Ichimura I, Oshino K, Yoshimura A, Yano Y, Hara Y
  • Journal Title: Journal of Periodontal Research Volume: 49 Issue: 3 Pages: 314-322
  • DOI: 10.1111/jre.12109
  • Peer Reviewed
• [Journal Article] A single nucleotide polymorphism in 3'-untranslated region contributes to the regulation of Toll-like receptor 4 translation. (2012)
  • Author(s): Sato K, Yoshimura A, Kaneko T, Ukai T, Ozaki Y, Nakamura H, Li X, Matsumura H, Hara Y, Ogata Y
  • Journal Title: Journal of Biological Chemistry Volume: 287 Issue: 30 Pages: 25163-72512
  • DOI: 10.1074/jbc.m111.338426
  • NAID: 120006985653
  • Peer Reviewed
• [Journal Article] Peptidoglycan and lipopolysaccharide synergistically enhance bone resorption and osteoclastogenesis (2012)
  • Author(s): Kishimoto T, Kaneko T, Ukai T, Yokoyama M, Ayon Haro R, Yoshinaga Y, Yoshimura A, Hara Y.
  • Journal Title: J Periodontal Res Volume: 47 Issue: 4 Pages: 446-454
  • DOI: 10.1111/j.1600-0765.2011.01452.x
  • Peer Reviewed
• [Journal Article] Aggregatibacter actinomycetemcomitans lipopolysaccharide regulates bone sialoprotein gene transcription. (2012)
  • Author(s): Li X, Zhou L, Takai H, Sasaki Y, Mezawa M, Li Z, Wang Z, Yang L, Wang S, Matsumura H, Kaneko T, Yoshimura A, Ogata Y.
  • Journal Title: J Cell Biochem Volume: 113 Issue: 9 Pages: 2822-2834
  • DOI: 10.1002/jcb.24157
  • Peer Reviewed
• [Journal Article] Assessment of the plasma/serum IgG test to screen for periodontitis. (2012)
  • Author(s): Kudo C
  • Journal Title: J Dent Res Volume: 91 Issue: 12 Pages: 1190-1195
  • DOI: 10.1177/0022034512461796
  • Peer Reviewed
• [Journal Article] テーパード毛歯ブラシの臨床効果に関する研究 (2012)
  • Author(s): 吉永美穂、鵜飼孝、吉永泰周、白石千秋、金子高士、岸本隆明、佐藤佳昌、吉村篤利、原宜興
  • Journal Title: 日本歯科保存学雑誌 Volume: 55 Pages: 158-164
  • NAID: 110009479992
  • Peer Reviewed
• [Presentation] ラット実験的歯周炎モデルを用いた歯周炎とインプラント周囲炎の病理組織学的比較 (2015)
  • Author(s): 髙森雄三, 中村弘隆, 藏本明子, 吉村篤利, 鵜飼 孝, 尾崎幸生, 白石千秋, 山下恭德, 泉 聡史, 小林弘樹, 小山美香, 原 宜興
  • Organizer: 日本歯科保存学会2015年度秋季学術大会
  • Place of Presentation: 文京シビックホール（東京都文京区）
  • Year and Date: 2015-11-12
• [Presentation] マウス骨髄マクロファージにおいてRANKL前刺激はTNF-a刺激による吸収活性を持つ破骨細胞の分化に重要な役割をはたす (2015)
  • Author(s): 山下恭德, 鵜飼孝, 中村弘隆, 小林弘樹, 高森雄三, 野口惠司, 吉村篤利, 原 宜興
  • Organizer: 平成27年度日本歯周病学会九州五大学・日本臨床歯周病学会九州支部合同研修会
  • Place of Presentation: アクロス福岡（福岡県福岡市）
  • Year and Date: 2015-11-08
• [Presentation] 歯石は NLRP3インフラマソームを活性化してヒトおよびマウス貪食細胞によるIL-1β産生を誘導する (2015)
  • Author(s): モンテネグロホルヘルイス、吉村篤利、ジャウディンエスエム、中村弘隆, 金子高士, 尾崎幸生, 原宜興
  • Organizer: 平成27年度日本歯周病学会九州五大学・日本臨床歯周病学会九州支部合同研修会
  • Place of Presentation: アクロス福岡（福岡県福岡市）
  • Year and Date: 2015-11-08
• [Presentation] Regulation of junctional epithelial relative gene in inflammation (2015)
  • Author(s): Nakayama Y, Kobayashi R, Matsui S, Matsumura H, Iwai Y, Noda K, Yamazaki M, Kurita-Ochiai T, Yoshimura A, Shinomura T, Ganss B, Ogata Y
  • Organizer: JADR
  • Place of Presentation: 福岡国際会議場（福岡県福岡市）
  • Year and Date: 2015-10-30
• [Presentation] Histopathological comparison of destruction between peri-implant and periodontal yissue in rats (2015)
  • Author(s): Takamori Y, Takamori A, Yoshinaga Y, Ukai T, Ozaki Y, Shiraishi C, Izumi S, Kobayashi H, Nakamura H, Yoshimura A, Hara Y
  • Organizer: 11th APSP meeting
  • Place of Presentation: Bali (Indonesia)
  • Year and Date: 2015-10-08
  • Int'l Joint Research
• [Presentation] Vascular endothelial cells promotes bone destruction in rat occlusal trauma (2015)
  • Author(s): Ukai T, Yamashita Y, Nakamura H, Yoshimura A, Hara Y
  • Organizer: 11th APSP meeting
  • Place of Presentation: Bali (Indonesia)
  • Year and Date: 2015-10-08
  • Int'l Joint Research
• [Presentation] Dental calculus induces IL-1β production through the NLRP3 inflammasome (2015)
  • Author(s): Yoshimura A, Montenegro JL, Ziauddin SM, Nakamura H, Kaneko T, Ozaki1 Y, Hara Y
  • Organizer: Toll 2015
  • Place of Presentation: Marbella (Spain)
  • Year and Date: 2015-09-30
  • Int'l Joint Research
• [Presentation] Resveratrol inhibits NLRP3 inflammasome-derived IL-1β secretion induced by dental calculus in murine macrophages (2015)
  • Author(s): モンテネグロホルヘルイス, 吉村篤利, ジャウディンエスエム, 中村弘隆, 金子高士, 尾崎幸生, 原宜興
  • Organizer: 第58回春秋日本歯周病学会学術大会
  • Place of Presentation: アクトシティ浜松（静岡県浜松市）
  • Year and Date: 2015-09-12
• [Presentation] Topical application of glycyrrhetinic acid into rat gingival sulcus inhibits periodontal destruction induced by lipopolisaccharide (2015)
  • Author(s): Takamori A, Yoshinaga Y, Ukai T, Nakamura H, Takamori Y, Yamashita Y, Izumi S, Kobayashi H, Shiraishi C, Hara Y
  • Organizer: International Academy of Periodontology Meeting
  • Place of Presentation: Santiago (Chile)
  • Year and Date: 2015-04-17
  • Int'l Joint Research
• [Presentation] Relationship between a single nucleotide polymorphism in the 3’-untranslated region of TLR4 and periodontal condition (2015)
  • Author(s): Lee H, Yoshimura A, Montenegro RJL, Ziauddin SM, Kuramoto A, Shiraishi C, Ukai T, Hara Y
  • Organizer: International Academy of Periodontology Meeting
  • Place of Presentation: Santiago (Chile)
  • Year and Date: 2015-04-17
  • Int'l Joint Research
• [Presentation] TLR2およびTLR4リガンド投与マウス歯肉における炎症性および抗炎症性サイトカインの発現 (2014)
  • Author(s): 尾崎幸生, 吉村篤利, 金子高士, 鵜飼 孝, 吉永泰周, Jorge Montenegro, Ziauddin SM, 白石千秋, 中村弘隆, 藏本明子, 原 宜興
  • Organizer: 日本歯科保存学会2014年度秋季学術大会
  • Place of Presentation: 山形テルサ（山形市）
  • Year and Date: 2014-10-30 – 2014-10-31
• [Presentation] ラットにおけるインプラント周囲炎と歯周炎発症の病理組織学的比較 (2014)
  • Author(s): 高森雄三，熱田 生，吉永泰周，藏本明子，野口惠司，泉 聡史，山下恭德， 鵜飼 孝，吉村篤利，原 宜興
  • Organizer: 日本歯周病学会2014年度秋季学術大会
  • Place of Presentation: 神戸国際展示場（神戸市）
  • Year and Date: 2014-10-19
• [Presentation] Dental calculus induces IL-1β production in murine macrophages through the NLRP3 inflammasome (2014)
  • Author(s): モンテネグロ・ホルヘ、吉村篤利、エスエム・ジャウディン、金子高士、原 宜興
  • Organizer: 日本歯周病学会2014年度秋季学術大会
  • Place of Presentation: 神戸国際展示場（神戸市）
  • Year and Date: 2014-10-19
• [Presentation] RANKL priming accelerates osteoclast formation with resorptive activity in TNF-alpha-stimulated murine bone marrow macrophages independent of RANKL (2014)
  • Author(s): Yamashita Y, Ukai T, Takamori Y, Noguchi S, Montenegro Raudales JL, Nakamura H, Ozaki Y, Shiraishi C, Yoshimura A, Hara Y
  • Organizer: 100th Anniversary meeting of American Academy of Periodontology
  • Place of Presentation: モスコンセンター （サンフランシスコ）
  • Year and Date: 2014-09-19 – 2014-09-22
• [Presentation] LPS 感作と歯肉溝滴下による長い上皮性付着破壊に関する実験病理組織学的検討 (2014)
  • Author(s): 野口惠司、吉村篤利、鵜飼孝、白石千秋、吉永美穂、吉永泰周、藏本明子、高森雄三、泉聡史、原宜興
  • Organizer: 日本歯科保存学会2014年度春季学術大会
  • Place of Presentation: 滋賀県立芸術劇場（大津市）
  • Year and Date: 2014-06-19 – 2014-06-20
• [Presentation] ROCK inhibitor Y-27632 maintains the proliferation ofconfluent human mesenchymal stem cells (2013)
  • Author(s): Kouhei Nakamura, Atsutoshi Yoshimura, Takashi Kaneko, Kayo Sato, Chiaki Shiraishi, Miho Yoshinaga, Hirotaka Nakamura, Yoshitaka Hara
  • Organizer: 10th Asian Pacific Society of Periodontology Meeting
  • Place of Presentation: 奈良県新公会堂（奈良市）
• [Presentation] 思春期に発症した下顎前歯歯肉退縮に結合組織移植と口腔前庭拡張術で対応した一症例 (2013)
  • Author(s): 吉村篤利
  • Organizer: 第56回秋季日本歯周病学会学術大会
  • Place of Presentation: 前橋市民文化会館（前橋市）
• [Presentation] 歯肉縁下プラークの Toll-like receptor (TLR)2 および TLR4 活性化能と歯周組織の状態との関連性について (2013)
  • Author(s): 佐藤佳昌、吉岡英将、吉村篤利、金子高士、原宜興
  • Organizer: 第139回日本歯科保存学会秋季学術大会
  • Place of Presentation: 秋田県総合生活文化会館（秋田市）
• [Presentation] 18β-グリチルレチン酸は LPS 誘導性実験的歯周炎を抑制する (2013)
  • Author(s): 藏本明子, 鵜飼孝, 中村弘隆, 吉永泰周, 髙森雄三, 野口惠司, 泉聡史, 白石千秋, 小野山美穂, 吉村篤利, 原宜興
  • Organizer: 第139回日本歯科保存学会秋季学術大会
  • Place of Presentation: 秋田県総合生活文化会館（秋田市）
• [Presentation] TNFα刺激により破骨細胞形成が促進される RANKL 前刺激条件の検討 (2013)
  • Author(s): 山下恭德, 鵜飼 孝, 吉村篤利, 金子高士, 白石千秋, 吉永美穂, 吉永泰周, 原 宜興
  • Organizer: 第139回日本歯科保存学会秋季学術大会
  • Place of Presentation: 秋田県総合生活文化会館（秋田市）
• [Presentation] Toll-Like Receptor 4発現におけるTLR4遺伝子3’側非翻訳領域の一塩基多型rs11536889の役割 (2012)
  • Author(s): 佐藤佳昌, 吉村篤利, 金子高士, 岸本隆明, 松村浩禎, 小方頼昌, 原 宜興
  • Organizer: 第136回日本歯科保存学会秋季学術大会
  • Place of Presentation: 宜野湾市
• [Presentation] T cell from mice immunized with peptidoglycan accerelates lipopolisacchride-induced osteoclastgnesis (2012)
  • Author(s): Yokoyama M, Ukai T, Kaneko T, Kishimoto T, Sato K, Shiraishi C, Ozaki Y, Yoshimura A, Hara Y
  • Organizer: 7th Congress of the European Federation of Periodontology
  • Place of Presentation: Vienna, Austria
• [Presentation] Analysis of the pro-inflammatory property of subgingival plaque (2012)
  • Author(s): Kayo Sato, Hidenobu Yoshioka, Atsutoshi Yoshimura, Takashi Kaneko, Yoshitaka Hara
  • Organizer: First International Conference on Porphyromonas gingivalis and Related Bacterial Species
  • Place of Presentation: Nagasaki, Japan
• [Presentation] ペプチドグリカンで感作したマウスのT細胞はLPS存在下で破骨細胞形成を促進する (2012)
  • Author(s): 横山美穂, 鵜飼 孝,山下恭徳,吉永泰周,中村弘隆,尾崎幸生,金子高士,吉村篤利,原 宜興
  • Organizer: 第55回秋季日本歯周病学会学術大会
  • Place of Presentation: つくば市
• [Presentation] Effects of rs11536889 G/C polymorphism on Toll-like receptor 4 expression (2012)
  • Author(s): Kayo Sato, Atsutoshi Yoshimura, Takashi Kaneko, Takaaki Kishimoto, Hiroyoshi Matsumura, Xinyue Li, Yorimasa Ogata, Yoshitaka Hara
  • Organizer: The 98th Annual Meeting of American Academy of Periodontology in collaboration with the Japanese Society of Periodontology
  • Place of Presentation: Los Angeles, USA
• [Presentation] Peptidoglycan and lipopolysaccharide synergistically enhance bone resorption and osteoclastogenesis (2012)
  • Author(s): Takashi Kaneko, Takaaki Kishimoto, Takashi Ukai, Miho Yokoyama, Yasunori Yoshimaga, Kayo Sato, Atsutoshi Yoshimura, Yoshitaka Hara
  • Organizer: The 98th Annual Meeting of American Academy of Periodontology in collaboration with the Japanese Society of Periodontology
  • Place of Presentation: Los Angeles, USA
• [Presentation] A single nucleotide polymorphism rs11536889 in 3’-untranslated region of TLR4 contributes to the regulation of Toll-like receptor 4 expression (2012)
  • Author(s): Atsutoshi Yoshimura, Kayo Sato, Takashi Kaneko, Xinyue Li, Hiroyoshi Matsumura, Yorimasa Ogata, Yoshitaka Hara
  • Organizer: The 12th Biennial International Endotoxin and Innate Immunity Society Meeting
  • Place of Presentation: Tokyo, Japan
• [Presentation] The crystals in dental calculus accelerate IL-1β production through activation of NLRP3 inflammasome in mouse macrophage and human peripheral polymorphonuclear leukocyte (2012)
  • Author(s): Nakamura H, Yoshimura A, Kaneko T, Latz E, HaraY
  • Organizer: The 12th Biennial International Endotoxin and Innate Immunity Society Meeting
  • Place of Presentation: Tokyo, Japan
• [Presentation] 歯石中のリン酸カルシウム結晶はNLRP3インフラマソームを活性化する (2012)
  • Author(s): 中村弘隆, 吉村篤利. 金子高士, Eicke Latz, 原 宜興
  • Organizer: 2012年度日本臨床歯周病学会九州支部・日本歯周病学会九州5大学合同研修会
  • Place of Presentation: 福岡市
• [Book] ザ・ペリオドントロジー 第２版 (2014)
  • Author(s): 吉村篤利、原宜興
  • Total Pages: 279
  • Publisher: 永末書店
• [Book] エンドトキシン・自然免疫研究 16 (2013)
  • Author(s): 吉村篤利、佐藤佳昌、金子高士、原宜興
  • Total Pages: 39
  • Publisher: 医学図書出版株式会社
• [Remarks] 長崎大学歯学部歯周病学分野ホームページ
  • URL: http://www.de.nagasaki-u.ac.jp/education/dept_perio.html
• [Remarks] 長崎大学 研究者総覧データベース
  • URL: http://research.jimu.nagasaki-u.ac.jp/IST
• [Remarks] 長崎大学歯学部歯周病学分野ホームページ
  • URL: http://www.de.nagasaki-u.ac.jp/education/dept_perio.html
• [Remarks] 長崎大学教員個人業績
• [Remarks] 長崎大学歯学部歯周病学分野ホームページ
  • URL: http://www.de.nagasaki-u.ac.jp/education/dept_perio.html
• [Remarks] 長崎大学教員個人業績
  • URL: http://gyoseki.jimu.nagasaki-u.ac.jp/IST?ISTActId=RESULTSJPDetail&ISTKidoKbn=&ISTErrorChkKbn=&ISTFormSetKbn=&ISTTokenChkKbn=&userId=770&search_nendo=