Investigation for a control method of neutrophil immunity

• Project/Area Number: 26293390
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Morphological basic dentistry
• Research Institution: Niigata University
• Principal Investigator: TERAO Yutaka 新潟大学, 医歯学系, 教授 (50397717)
• Co-Investigator(Kenkyū-buntansha): 小田 真隆 新潟大学, 医歯学系, 准教授 (00412403) ; 土門 久哲 新潟大学, 医歯学系, 助教 (00594350)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000); Fiscal Year 2016: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2015: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
• Keywords: 好中球 / 誤嚥性肺炎 / 肺炎レンサ球菌

Outline of Final Research Achievements

Streptococcus penumoniae is a major pathogen that causes elderly pneumonia. S. pneunoniae expresses several toxins and one of them possesses cytolytic activity. However, the pneumolysin is located in the cytosol of the pneumococcus and this bacteria doesn’t have any pomp system to release the pneumolysin. The main contribution of this present study is the elucidation of the mechanism by which S. pneumoniae recruits host enzymes to promote the progression of pneumococcal infection. We believe that this contribution is theoretically and practically relevant because we demonstrate that the pneumococcal pore-forming toxin pneumolysin selectively degrades neutrophils to promote the release of neutrophil elastase, which subsequently targets alveolar epithelial cells and macrophages, but exhibits no cytotoxicity toward S. pneumoniae.

Research Products

• [Journal Article] Differential Expression and Roles of Secreted Frizzled-Related Protein and the Wingless Homolog Wnt5a in Periodontitis. (2017)
  • Author(s): Maekawa T, Kulwattanaporn P, Hosur K, Domon H, Oda M, Terao Y, Maeda T, Hajishengallis G.
  • Journal Title: J Dent Res Volume: 96(5) Issue: 5 Pages: 571-577
  • DOI: 10.1177/0022034516687248
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Milk fat globule epidermal growth factor 8 inhibits periodontitis in non-human primates and its gingival crevicular fluid levels can differentiate periodontal health from disease in humans (2017)
  • Author(s): Kajikawa T., Meshikhes F., Maekawa T., Hajishengallis E., Hosur K. B., Abe T., Moss K., Chavakis T., Hajishengallis G.
  • Journal Title: J Clin Periodontol Volume: jcpe.12707 Issue: 5 Pages: 472-483
  • DOI: 10.1111/jcpe.12707
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Antimicrobial activity of ethylene-vinyl acetate containing bioactive filler against oral bacteria (2016)
  • Author(s): Nagai K, Domon H, Oda M, Shirai T, Ohsumi T, Terao Y, Arai Y
  • Journal Title: Dent Mater J Volume: 480 Pages: 173-179
  • NAID: 130006224952
  • Peer Reviewed
• [Journal Article] Streptococcus pneumoniae disrupts pulmonary immune defence via elastase release following pneumolysin-dependent neutrophil lysis (2016)
  • Author(s): Domon H, Oda M, Maekawa T, Nagai K, Takeda W, Terao Y
  • Journal Title: Sci Rep Volume: 6 Pages: 38013-38013
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Adverse Influences of Antimicrobial Strategy against Mature Oral Biofilm (2016)
  • Author(s): Takenaka S, Oda M, Domon H, Wakamatsu R, Ohsumi T, Terao Y, Noiri Y
  • Journal Title: Microbial Biofilms - Importance and Applications Volume: 18
  • DOI: 10.5772/63564
  • ISBN: 9789535124351, 9789535124368
  • Peer Reviewed
• [Journal Article] Vizantin inhibits bacterial adhesion without affecting bacterial growth and causes Streptococcus mutans biofilm to detach by altering its internal architecture (2016)
  • Author(s): Takenaka S, Oda M, Domon H, Ohsumi T, Suzuki Y, Ohshima H, Yamamoto H, Terao Y, Noiri Y
  • Journal Title: Biochem Biophys Res Commun Volume: 480 Pages: 173-179
  • Peer Reviewed
• [Journal Article] シリーズバイオセーフティ (2016)
  • Author(s): 寺尾 豊
  • Journal Title: BMSAジャーナル Volume: 28(3) Pages: 99-103
• [Journal Article] 劇症型溶血性レンサ球菌感染症（人食いバクテリア） (2016)
  • Author(s): 寺尾 豊，黒澤美絵
  • Journal Title: 感染・炎症・免疫 Volume: 7 Pages: 76-78
• [Journal Article] Chemical hybridization of Vizantin and Lipid A to generate a novel LPS antagonist. (2016)
  • Author(s): Yamamoto H, Oda M, Kanno M, Tamashiro S, Tamura I, Yoneda T, Yamasaki N, Domon H, Nakano M, Takahashi H, Terao Y, Kasai Y, Imagawa H.
  • Journal Title: Chem Pham Bull Volume: 64 Pages: 246-257
  • NAID: 130005131585
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Anti-biofilm and bactericidal effects of Magnolia bark-derived magnolol and honokiol on Streptococcus mutans. (2016)
  • Author(s): Sakaue Y, Domon H, Oda M, Takenaka S, Kubo M, Fukuyama Y, Okiji T, Terao Y.
  • Journal Title: Microbiol Immunol Volume: 60 Pages: 10-16
  • NAID: 40020725379
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Streptococcus pyogenes CAMP factor attenuates phagocytic activity of RAW 264.7 cells. (2016)
  • Author(s): Kurosawa M, Oda M, Domon H, Saitoh I, Hayasaki H, Terao Y.
  • Journal Title: Microb Infect Volume: 18 Pages: 118-127
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Poor survival of Methicillin-resistant Staphylococcus aureus on inanimate objects in the public spaces. (2016)
  • Author(s): Domon H, Uehara Y, Oda M, Seo H, Kubota N, Terao Y.
  • Journal Title: MicrobiologyOpen Volume: 5 Pages: 39-46
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Membrane-binding mechanism of Clostridium perfringens alpha-toxin. (2015)
  • Author(s): Oda M, Terao Y, Sakurai J, Nagahama M.
  • Journal Title: Toxins Volume: 7 Pages: 5268-5275
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Total synthesis of palau’amine. (2015)
  • Author(s): Namba K, Takeuchi K, Kaihara Y, Oda M, Nakayama A, Nakayama A, Yoshida M, Tanino K.
  • Journal Title: Nat Commun Volume: 6 Pages: 8731-8731
  • NAID: 120006999407
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Identification of the replication region in pBCNF5603, a bacteriocin-encoding plasmid, in the enterotoxigenic Clostridium perfringens strain F5603. (2015)
  • Author(s): Miyamoto K, Seike S, Takagishi T, Okui K, Oda M, Takehara M, Nagahama M.
  • Journal Title: BMC Microbial Volume: 15 Pages: 118-118
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Tetranorsesquiterpenoids and santalane-type sesquiterpenoids from Illicium lanceolatum and their antimicrobial activity against the oral pathogen Porphyromonas gingivalis. (2015)
  • Author(s): Kubo M, Nishikawa Y, Harada K, Oda M, Huang JM, Domon H, Terao Y, Fukuyama Y.
  • Journal Title: J Nat Prod Volume: 78 Pages: 1466-1469
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Clostridium perfringens alpha-toxin induces GM1a clustering and TrkA phosphorylation in the host cell membrane. (2015)
  • Author(s): Takagishi T, Oda M, Kabura M, Kurosawa M, Tominaga K, Urano S, Ueda Y, Kobayashi K, Kobayashi T, Sakurai J, Terao Y, Nagahama M.
  • Journal Title: PLoS one Volume: 10
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Clostridium perfringens alpha-toxin induces GM1a clustering and TrkA phosphorylation in the host cell membrane. (2015)
  • Author(s): Takagishi, T., Oda, M., Kabura, M., Kurosawa, M., Tominaga, K., Urano, S., Ueda, Y.,Kobayashi, K., Kobayashi, T., Sakurai, J., Terao, Y., and Nagahama, M.
  • Journal Title: PLoS one Volume: in press
  • Peer Reviewed
• [Journal Article] ndoplasmic reticulum stress response and bone loss in experimental periodontitis in mice. (2015)
  • Author(s): Yamada, H., Nakajima, T., Domon, H., Honda, T., and Yamazaki, K.
  • Journal Title: J. Periodontal Res Volume: in press
  • Peer Reviewed
• [Journal Article] esidual structure of Streptococcus mutans biofilm following complete disinfection favors secondary bacterial adhesion and biofilm re-development. (2015)
  • Author(s): Ohsumi, T., Takenaka, S., Wakamatsu, R., Sakaue, Y., Narisawa, N., Senpuku, H., Ohshima, H., Terao, Y., and Okiji, T.
  • Journal Title: PLoS one Volume: 10
  • Peer Reviewed
• [Journal Article] Vizantin inhibits endotoxin-mediated immune responses via the Toll-like receptor 4/MD-2 complex. (2014)
  • Author(s): Oda, M., Yamamoto, H., Shibutani, M., Nakano, M., Yabiku, K., Tarui, T., Kameyama, N., Shirakawa, D., Obayashi, S., Watanabe, N., Nakase, H., Suenaga, M., Matsunaga, Y., Nagahama, M., Takahashi, H., Imagawa, H., Kurosawa, M., Terao, Y., Nishizawa, M., and Sakurai, J.:
  • Journal Title: J. Immunol Volume: 193 Pages: 4507-4514
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Age-related alterations in gene expression of gingival fibroblasts stimulated with Porphyromonas gingivalis. (2014)
  • Author(s): Domon, H., Nakajima, T., Tabeta, K., and Yamazaki, K.
  • Journal Title: J. Periodontal Res. Volume: 49 Pages: 536-543
  • Peer Reviewed
• [Presentation] Differential Expression and Roles of Sfrp5 and Wnt5a in Periodontitis (2017)
  • Author(s): Maekawa T, Kulwattanaporn P, Hosur K, Domon H, Terao Y, Maeda T, Hajishengallis G
  • Organizer: 95th General Session & Exhibition of the IADR
  • Place of Presentation: San Francisco, CA, USA
  • Year and Date: 2017-03-24
  • Int'l Joint Research
• [Presentation] 肺炎球菌感染時における好中球エラスターゼのin vitro機能解析 (2017)
  • Author(s): 土門久哲，前川知樹，永井康介，寺尾 豊
  • Organizer: 第90回日本細菌学会総会
  • Place of Presentation: 仙台国際ホール（宮城県仙台市）
  • Year and Date: 2017-03-20
• [Presentation] 誤嚥性肺炎に対する新規感染制御法の開発に向けた多次元解析 (2017)
  • Author(s): 土門久哲
  • Organizer: 第１回D3研究交流会
  • Place of Presentation: ときめいと（新潟県新潟市）
  • Year and Date: 2017-01-24
• [Presentation] 血管が作り出す生体由来の分子による歯周病マーカーの開発と応用研究 (2017)
  • Author(s): 前川知樹
  • Organizer: 第１回D3研究交流会
  • Place of Presentation: ときめいと（新潟県新潟市）
  • Year and Date: 2017-01-24
• [Presentation] 食品由来ペプチドを用いた 誤嚥性肺炎感染制御法の検索 (2016)
  • Author(s): 土門久哲
  • Organizer: 第1回U-goサロン
  • Place of Presentation: 新潟大学（新潟県新潟市）
  • Year and Date: 2016-12-05
• [Presentation] 内因性Del-1分子による炎症性骨吸収の制御メカニズム解析とサルの応用研究 (2016)
  • Author(s): 前川知樹
  • Organizer: 第19回骨代謝研究会
  • Place of Presentation: 慶応大学（東京都新宿区）
  • Year and Date: 2016-11-26
  • Invited
• [Presentation] Keystone細菌と生体の相互作用 (2016)
  • Author(s): 前川知樹
  • Organizer: 第69回日本細菌学会関西支部総会
  • Place of Presentation: 大阪市立大学（大阪府堺市）
  • Year and Date: 2016-11-19
  • Invited
• [Presentation] Streptococcus pyogenesによる皮膚病変の形成機構に関する解析 (2016)
  • Author(s): 毛利泰士，住友倫子，松岡悠美，本多真理子，山口雅也，寺尾 豊，中田匡宣，川端重忠
  • Organizer: 第69回日本細菌学会関西支部総会
  • Place of Presentation: 大阪市立大学（大阪府堺市）
  • Year and Date: 2016-11-19
• [Presentation] 肺炎球菌性肺炎の重症化メカニズムの分子解析 (2016)
  • Author(s): 土門久哲，小田真隆，川端重忠，寺尾 豊
  • Organizer: 第65回日本感染症学会東日本地方会学術集会
  • Place of Presentation: 朱鷺メッセ（新潟県新潟市）
  • Year and Date: 2016-10-27
• [Presentation] 結核表層糖脂質誘導体のStreptococcus mutansバイオフィルム形成に与える影響 (2016)
  • Author(s): 竹中彰治，小田真隆，黒澤美絵，土門久哲，大墨竜也，寺尾 豊，野杁由一郎
  • Organizer: 日本歯科保存学会2016年度秋期学術大会
  • Place of Presentation: 松本歯科大学（長野県塩尻市）
  • Year and Date: 2016-10-27
• [Presentation] A群レンサ球菌のPI3K/Akt活性化因子を介した咽頭上皮細胞株への付着・侵入メカニズムの解析 (2016)
  • Author(s): 黒澤美絵，小田真隆，土門久哲，齊藤一誠，早﨑治明，寺尾 豊
  • Organizer: 第58回歯科基礎医学会
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市）
  • Year and Date: 2016-08-25
• [Presentation] Porphyromonas gingivalisは補体C5aとTLRを利用して免疫系から回避する (2016)
  • Author(s): 前川知樹，前田健康，寺尾 豊
  • Organizer: 第58回歯科基礎医学会
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市）
  • Year and Date: 2016-08-25
• [Presentation] Streptococcus pneumoniaeの肺組織障害におけるカスケード機構の解析 (2016)
  • Author(s): 寺尾 豊，土門久哲
  • Organizer: 第48回レンサ球菌研究会
  • Place of Presentation: 長崎大学（長崎県長崎市）
  • Year and Date: 2016-07-09
  • Invited
• [Presentation] 肺炎球菌の自己融解に起点を発する肺傷害のカスケード機構 (2016)
  • Author(s): 土門久哲，小田真隆，寺尾 豊
  • Organizer: 第55回新潟化学療法研究会
  • Place of Presentation: ANAクラウンプラザホテル（新潟県新潟市）
  • Year and Date: 2016-07-02
• [Presentation] Inhibition of periodontitis in non-human primates by a locally administered complement C3 inhibitor (2016)
  • Author(s): Maekawa T, Maeda T, Hajishengallis E
  • Organizer: 94th General Session & Exhibition of the IADR
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2016-05-22
  • Int'l Joint Research
• [Presentation] 多機能性糖脂質によるマクロファージ細胞外捕獲網形成機構の解明 (2016)
  • Author(s): 小田真隆，黒澤美絵，土門久哲，寺尾 豊
  • Organizer: 第89回日本細菌学会総会
  • Place of Presentation: 大阪国際交流センター 大ホール（大阪府大阪市）
  • Year and Date: 2016-03-23
• [Presentation] 肺炎球菌による肺組織傷害誘導メカニズムの解析 (2016)
  • Author(s): 土門久哲，坂上雄樹，小田真隆，山口雅也，川端重忠，寺尾 豊
  • Organizer: 第89回日本細菌学会総会
  • Place of Presentation: 大阪国際交流センター 大ホール（大阪府大阪市）
  • Year and Date: 2016-03-23
• [Presentation] Streptococcus pyogenesの咽頭上皮細胞株への付着・侵入におけるCAMP factorの役割 (2016)
  • Author(s): 黒澤美絵，小田真隆，土門久哲，寺尾 豊
  • Organizer: 第89回日本細菌学会総会
  • Place of Presentation: 大阪国際交流センター 大ホール（大阪府大阪市）
  • Year and Date: 2016-03-23
• [Presentation] 多機能性糖脂質によるマクロファージMETs形成メカニズムの解析 (2015)
  • Author(s): 小田真隆，黒澤美絵，土門久哲，寺尾 豊
  • Organizer: 第57回歯科基礎医学会学術大会
  • Place of Presentation: 朱鷺メッセ（新潟県新潟市）
  • Year and Date: 2015-09-11
• [Presentation] 肺炎球菌による宿主細胞の細胞死誘導能の解析 (2015)
  • Author(s): 土門久哲，坂上雄樹，小田真隆，山口雅也，川端重忠，寺尾 豊
  • Organizer: 第57回歯科基礎医学会学術大会
  • Place of Presentation: 朱鷺メッセ（新潟県新潟市）
  • Year and Date: 2015-09-11
• [Presentation] Streptococcus pyogenes CAMP factorのRAW264.7細胞に対する病原性解析 (2015)
  • Author(s): 黒澤美絵，小田真隆，土門久哲，寺尾豊
  • Organizer: 第88回日本細菌学会総会
  • Place of Presentation: 岐阜，長良川国際会議場
  • Year and Date: 2015-03-26 – 2015-03-28
• [Presentation] イメージングと細菌学研究 (2014)
  • Author(s): 寺尾豊
  • Organizer: 第67回 日本細菌学会中国・四国支部総会
  • Place of Presentation: 徳島，徳島文理大学薬学部
  • Year and Date: 2014-10-20
  • Invited
• [Presentation] Streptococcus mutansバイオフィルムに対する植物由来抽出物の検索 (2014)
  • Author(s): 坂上雄樹，土門久哲，小田真隆，興地隆史，寺尾豊
  • Organizer: 第51回日本細菌学会中部支部総会
  • Place of Presentation: 金沢，北陸大学薬学部
  • Year and Date: 2014-10-17 – 2014-10-18
• [Presentation] Streptococcous pyogenes CAMP factorの免疫担当細胞に対する病原性解析 (2014)
  • Author(s): 黒澤美絵，小田真隆，土門久哲，寺尾 豊
  • Organizer: 第51回日本細菌学会中部支部総会
  • Place of Presentation: 金沢，北陸大学薬学部
  • Year and Date: 2014-10-17 – 2014-10-18
• [Presentation] 多機能性糖脂質の自然免疫活性化メカニズムの解明 (2014)
  • Author(s): 小田真隆，山本博文，黒澤美絵，土門久哲，寺尾 豊
  • Organizer: 第51回日本細菌学会中部支部総会
  • Place of Presentation: 金沢，北陸大学薬学部
  • Year and Date: 2014-10-17 – 2014-10-18
• [Presentation] 慢性炎症性疾患におけるT L R シグナル抑制因子の解析 (2014)
  • Author(s): 土門久哲，坂上雄樹，小田真隆，寺尾 豊
  • Organizer: 51回日本細菌学会中部支部総会
  • Place of Presentation: 金沢，北陸大学薬学部
  • Year and Date: 2014-10-17 – 2014-10-18
• [Presentation] A群レンサ球菌CAMPファクターのマクロファージに対する病原性解析 (2014)
  • Author(s): 小田真隆，黒澤美絵，土門久哲，寺尾 豊
  • Organizer: 第56回歯科基礎医学会学術大会・総会
  • Place of Presentation: 福岡，福岡国際会議場
  • Year and Date: 2014-09-26 – 2014-09-27
• [Presentation] 歯周炎におけるTLR シグナル抑制因子の解析 (2014)
  • Author(s): 土門久哲，小田真隆，寺尾 豊
  • Organizer: 第56回歯科基礎医学会学術大会・総会
  • Place of Presentation: 福岡，福岡国際会議場
  • Year and Date: 2014-09-26 – 2014-09-27
• [Presentation] 合成糖脂質のStreptococcus mutansバイオフィルムに対する作用 (2014)
  • Author(s): 黒澤美絵，小田真隆，土門久哲，寺尾 豊
  • Organizer: 第56回歯科基礎医学会学術大会・総会
  • Place of Presentation: 福岡，福岡国際会議場
  • Year and Date: 2014-09-26 – 2014-09-27
• [Presentation] Streptococcus mutansに対する植物由来抽出物の殺菌ならびに抗バイオフィルム効果の検討 (2014)
  • Author(s): 坂上雄樹，土門久哲，小田真隆，興地隆史，寺尾 豊
  • Organizer: 第56回歯科基礎医学会学術大会・総会
  • Place of Presentation: 福岡，福岡国際会議場
  • Year and Date: 2014-09-26 – 2014-09-27
• [Book] 口腔微生物学・免疫学 第４版 (2015)
  • Author(s): 川端重忠，小松澤均，大原直也，寺尾 豊，浜田茂幸編
  • Total Pages: 303
  • Publisher: 医歯薬出版
• [Book] 日本歯科評論：ナノスケールの研究を歯科医学に (2014)
  • Author(s): 寺尾 豊
  • Total Pages: 181
  • Publisher: ヒョーロン・パブリッシャーズ社
• [Remarks] 研究室HPトップ
  • URL: http://www.dent.niigata-u.ac.jp/microbio/microbio.html
• [Remarks] 肺炎球菌の病原因子および細菌性肺炎重症化機構の解析
  • URL: http://www.niigata-univ-mid.net/study/index4.html
• [Remarks] 感染免疫現象のバイオイメージング解析
  • URL: http://www.niigata-univ-mid.net/study/index.html
• [Remarks] 研究者の作成したHP
  • URL: http://www.dent.niigata-u.ac.jp/microbio/microbio.html
• [Remarks] 本申請研究の成果HP
  • URL: http://www.niigata-univ-mid.net/study/index.html