Infection control with secretory leukocyte protease inhibitor (SLPI) via the inhibitory effect on the invasion of periodontopathic bacteria across gingival epithelial barrier

• Project/Area Number: 15K11020
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Morphological basic dentistry
• Research Institution: Kansai Women's Junior College (2016-2017); Iwate Medical University (2015)
• Principal Investigator: Kimura Shigenobu 関西女子短期大学, その他部局等, 教授 (10177917)
• Co-Investigator(Kenkyū-buntansha): 根本 優子 長崎大学, 医歯薬学総合研究科(歯学系), 准教授 (10164667) ; 石河 太知 岩手医科大学, 歯学部, 助教 (10569247) ; 佐々木 実 岩手医科大学, 歯学部, 教授 (40187133) ; 下山 佑 岩手医科大学, 歯学部, 講師 (90453331)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: SLPI / 感染制御 / 歯周病原細菌 / 組織侵入抑制作用 / 感染制御機構 / 歯周病原性細菌

Outline of Final Research Achievements

In this study using the quantitation assays of bacteria and FITC-dextran, we assessed the invasion mechanism of the periodontopathic bacteria across gingival epithelial barrier through two putative routes (transcellular and paracellular routes), and assessed the inhibitory effect of the secretory leukocyte protease inhibitor (SLPI). The results indicated that all the periodontopathic bacteria tested could invade significantly across gingival epithelial barrier through the transcellular route, although P. gingivalis utilized the both routes. The SLPI could not show the inhibitory effect on the invasion of P. gingivalis across gingival epithelial barrier, whereas SLPI showed a direct inhibitory effect on the P. gingivalis protease of Lys-gingipain. Thus, the infection control with SLPI by itself could not be sufficient for the bacterial invasion across gingival epithelial barrier.

Research Products

• [Journal Article] 歯周病原細菌の歯肉上皮バリア突破能 (2017)
  • Author(s): 髙橋 晋平, 下山 佑, 石河 太知, 佐々木 大輔, 木村 重信, 八重柏 隆
  • Journal Title: 岩医大歯誌 Volume: 41 Pages: 1-11
  • NAID: 130006837470
  • Peer Reviewed
• [Journal Article] Degradation of Incretins and Modulation of Blood Glucose Levels by Periodontopathic Bacterial Dipeptidyl Peptidase 4. (2017)
  • Author(s): Ohara-Nemoto, Y., Nakasato, M., Shimoyama, Y., Baba, T., Kobayakawa, T., Ono, T., Yaegashi, T., Kimura, S., Nemoto, T.K.
  • Journal Title: Infection and Immunity Volume: 85 Issue: 9
  • DOI: 10.1128/iai.00277-17
  • NAID: 120006987494
  • Peer Reviewed / Open Access
• [Journal Article] Dominant prevalence of Porphyromonas gingivalis fimA types Ⅰ and Ⅳ in healthy Japanese children. (2017)
  • Author(s): Shimoyama, Y., Ohara-Nemoto, Y., Kimura, M., Nemoto, T.K., Tanaka, M. and Kimura, S.
  • Journal Title: Journal of Dental Sciences Volume: 12 Pages: 213-219
  • Peer Reviewed / Open Access
• [Journal Article] A Porphyromonas gingivalis periplasmic novel exopeptidase, acylpeptidyl oligopeptidase, releases N-acylated di- and tri-peptides from oligopeptides. (2016)
  • Author(s): Nemoto, T.K., Ohara-Nemoto, Y., Bezerra, G. A., Shimoyama, Y. and Kimura, S.
  • Journal Title: J. Biol. Chem. Volume: 291 Issue: 11 Pages: 5913-5925
  • DOI: 10.1074/jbc.m115.687566
  • NAID: 120006986807
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Influences of the butyric acid produced by periodontopathic bacteria on ameloblastoma. (2018)
  • Author(s): Ishikawa T., Shimoyama Y., Kodama Y., Kimura S. and Sasaki M.
  • Organizer: 第91回日本細菌学会総会
• [Presentation] Invasion mechanism of periodontopathic bacteria across gingival epithelial barrier. (2017)
  • Author(s): Takahashi S., Shimoyama Y., Ishikawa T., Sasaki D., Sasaki M., Kimura S. and Yaegashi T.
  • Organizer: 第90回日本細菌学会総会
• [Presentation] プロトン輸送ATPaseを標的とした抗う蝕化合物の探索． (2017)
  • Author(s): 泉澤信太郎，関谷瑞樹，櫛桁安生，芳賀雅人，下山 佑，木村重信，佐々木由香，岩本昌子，中西真弓．
  • Organizer: 日本薬学会 第137年会
• [Presentation] Dipeptidyl-peptidase 4 from Porphyromona gingivalis and Tannerella forsythia, and the hydrolyzing activity toward the incretin. (2017)
  • Author(s): Nakasato M., Shimoyama Y., Ohara-Nemoto Y., Kimura S., Sasaki D., Ito S., Sasaki M. and Yaegashi T.
  • Organizer: 第60回春季日本歯周病学会学術大会
• [Presentation] Streptococcus mutans の耐酸性におけるF-ATPaseの重要性． (2017)
  • Author(s): 関谷瑞樹，泉澤信太郎，櫛桁安生，芳賀雅人，下山 佑，佐々木実，木村重信，佐々木由香，岩本昌子，中西真弓．
  • Organizer: 第90回日本生化学会大会
• [Presentation] Invasion mechanism of ‘red complex species’ across the gingival epithelial barrier. (2016)
  • Author(s): Takahashi S., Ishikawa T., Shimoyama Y., Sasaki D., Kimura S. and Yaegashi T.
  • Organizer: The 102nd Annual Meeting of the American Academy of Periodontology in collaboration with Japanese Society of Periodontology and Japanese Academy of Clinical Periodontology
  • Place of Presentation: San Diego, CA, U.S.A.
  • Year and Date: 2016-09-10
  • Int'l Joint Research
• [Presentation] Porphyromonas gingivalis DPP4によるインクレチンの分解. (2016)
  • Author(s): 下山 佑，根本優子，石河太知，佐々木 実，根本孝幸，木村重信
  • Organizer: 第70回日本細菌学会 東北支部総会
  • Place of Presentation: 十和田，青森
  • Year and Date: 2016-08-18
• [Presentation] Characterization of dipeptidyl-peptidase 4 from Tannerella forsythia. (2016)
  • Author(s): Nakasato M., Shimoyama Y., Ohara-Nemoto Y., Nemoto T.K., Sasaki D., Yaegashi T. and Kimura S.
  • Organizer: ASM microbe 2016
  • Place of Presentation: Boston, MA, U.S.A.
  • Year and Date: 2016-06-16
  • Int'l Joint Research
• [Presentation] Degradation of incretin by the prokaryotic dipeptidyl-peptidase 4 from Porphyromonas gingivalis. (2016)
  • Author(s): Shimoyama Y., Ohara-Nemoto Y., Nemoto T.K., Nakasato M., Ishikawa T., Sasaki M.and Kimura S.
  • Organizer: ASM microbe 2016
  • Place of Presentation: Boston, MA, U.S.A.
  • Year and Date: 2016-06-16
  • Int'l Joint Research
• [Presentation] Quantification of mutans streptococci in children’s plaques and its relationship to the caries prevalence. (2016)
  • Author(s): Makinae T, Sakurai M, Shimoyama Y, Oikawa R, Kimura S, Tanaka M.
  • Organizer: 第10回アジア小児歯科学会・第54回日本小児歯科学会
  • Place of Presentation: Tokyo
  • Year and Date: 2016-05-26
  • Int'l Joint Research
• [Presentation] 歯周病原性細菌'red complex species'のビルレンス因子としてのプロテアーゼ (2016)
  • Author(s): 下山 佑，根本優子，中里茉那美，根本孝幸，高橋晋平，石河太知，佐々木大輔，八重柏 隆，佐々木 実，木村重信
  • 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（大阪）
  • Year and Date: 2016-03-23
• [Presentation] 歯周病原性細菌の上皮バリア突破機構． (2015)
  • Author(s): 高橋晋平，石河太知，下山 佑，八重柏 隆，佐々木 実，木村重信
  • Organizer: 第69回 日本細菌学会 東北支部総会
  • Place of Presentation: 郡山（福島県）
  • Year and Date: 2015-08-21