Establishment of intestinal peptide delivery system based on lactic acid bacteria and the therapeutic application for inflammatory bowel disease

• Project/Area Number: 24658099
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Applied biochemistry
• Research Institution: Fukuoka University
• Principal Investigator: MIAKE Fumio 福岡大学, 薬学部, 教授 (50248522)
• Co-Investigator(Kenkyū-buntansha): KASHIGE Nobuhiro 福岡大学, 薬学部, 教授 (80185751) ; SATHO Tomomitsu 福岡大学, 薬学部, 助教 (90369025)
• Research Collaborator: HIRAMATSU Yukihiro 福岡大学, 大学院・薬学研究科, 大学院生
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 乳酸菌 / CTB-YVAD融合体 / 抗炎症作用 / 炎症性腸疾患 / CTB-YVAD複合体

Research Abstract

Recombinant lactic acid bacteria (LAB) are used as bacterial vectors to deliver functional peptides to the intestine, and cholera toxin B subunit (CTB) can translocate into intestinal epithelial cells through GM1 ganglioside. To deliver the YVAD peptide, which has potential as a therapeutic agent for inflammatory bowel disease (IBD), to the intestine, we constructed LAB secreting a recombinant fusion protein of CTB with YVAD (CTB-YVAD). The present study demonstrated that CTB-YVAD bind to GM1 ganglioside, translocate into human intestinal epithelial cell line, and show the anti-inflammatory effects. Taken together, we showed potencies of peptide delivery system to the intestine used LAB and CTB, and new therapeutic agent for IBD used LAB secreting CTB-YVAD.

Research Products

• [Journal Article] Recombinant fusion protein of cholera toxin B subunit with YVAD secreted by Lactobacillus casei inhibits lipopolysaccharide- induced caspase- 1 activation and subsequent IL- 1 beta secretion in Caco- 2 cells (2014)
  • Author(s): Yukihiro Hiramatsu, Masatatsu Yamamoto, Tomomitsu Satho, Keiichi Irie, Akiko Kai, Saori Uyeda, Yuki Fukumitsu, Akihisa Toda, Takeshi Miyata, Fumio Miake, Takeshi Arakawa, Nobuhiro Kashige
  • Journal Title: BMC Biotechnology Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Expression and secretion of cholera toxin B subunit in lactobacilli (2013)
  • Author(s): Takahiro Okuno, Nobuhiro Kashige, Tomomitsu Satho, Keiichi Irie, Yukihiro Hiramatsu, Tanjina Sharmin, Yuki Fukmits, Saori Uyeda, Seitaro Yamada, Tetsuya Harakuni, Takeshi Miyata, Takeshi Arakawa, Masumi Imoto, Akihisa Toda, Yukihiko Nakashima, Fumio Miake
  • Journal Title: Biological Pharmaceutical Bulletin Volume: 36(6) Pages: 952-958
  • NAID: 130003361440
  • URL: https://www.jstage.jst.go.jp/article/bpb/36/6/36_b12-01021/_article
  • Peer Reviewed
• [Journal Article] Differences in TLR9-dependent inhibitory effects of H_2O_2-induced IL-8 secretion and NF-kappa B/I kappa B-alpha system activation by genomic DNA from five Lactobacillus species (2013)
  • Author(s): Yukihiro Hiramatsu, Tomomitsu Satho, Keiichi Irie, Shota Shiimura, Takahiro Okuno, Tanjina Sharmin, Yuki Fukumitsu, Saori Uyeda, Yukihiko Nakashima, Fumio Miake, Nobuhiro Kashige
  • Journal Title: Microbes and Infection Volume: 15(2) Issue: 2 Pages: 96-104
  • DOI: 10.1016/j.micinf.2012.11.003
  • Peer Reviewed
• [Journal Article] Expression and secretion of cholera toxin B subunit in lactobacilli (2013)
  • Author(s): Takahiro Okuno, Nobuhiro Kashige, Tomomitsu Satho, Keiichi Irie, Yukihiro Hiramatsu, Tanjina Sharmin, Yuki Fukmits, Saori Uyeda, Seitaro Yamada, Tetsuya Harakuni, Takeshi Miyata, Takeshi Arakawa, Masumi Imoto, Akihisa Toda, Yukihiko Nakashima, Fumio Miake
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 36(6) Pages: 952-958
  • NAID: 130003361440
  • Peer Reviewed
• [Journal Article] Expression and secretion of cholera toxin B subunit in lactobacilli (2013)
  • Author(s): Takahiro Okuno, Nobuhiro Kashige, Tomomitsu Satho. et al.
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 印刷中
  • NAID: 130003361440
  • Peer Reviewed
• [Journal Article] Recombinant fusion protein of cholera toxin B subunit with YVAD secreted by Lactobacillus casei inhibits lipopolysaccharide-induced caspase-1 activation and subsequent IL-1 beta secretion in Caco-2 cells
  • Author(s): Yukihiro Hiramatsu, Masatatsu Yamamoto, Tomomitsu Satho, Keiichi Irie, Akiko Kai, Saori Uyeda, Yuki Fukumitsu, Akihisa Toda, Takeshi Miyata, Fumio Miake, Takeshi Arakawa, Nobuhiro Kashige
  • Journal Title: BMC Biotechnology Volume: (In press)
• [Presentation] 乳酸菌由来DNAの腸管における抗炎症作用 (2013)
  • Author(s): 平松征洋、佐藤朝光、入江圭一、百武美香、見明史雄、鹿志毛信広
  • Organizer: 第30回日本薬学会九州支部大会
  • Place of Presentation: 長崎国際大学
  • Year and Date: 2013-12-07
• [Presentation] マウスにおけるDSS誘導性大腸炎の病態とTREM-1/TREM-2の発現量比の一致 (2013)
  • Author(s): 江川さおり、百武美香、中村智美、平松征洋、上田紗織、入江圭一、佐藤朝光、中島幸彦、三島健一、鹿志毛信広、見明史雄
  • Organizer: 第86回日本生化学会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2013-09-11
• [Presentation] Oligodeoxynucleotide 5'- TTTTGCCG- 3' inhibits intestinal inflammation (2013)
  • Author(s): Yukihiro Hiramatsu, Tomomitsu Satho, Keiichi Irie, Shota Shiimura, Yukihiko Nakashima, Fumio Miake, Nick Carpino, Nobuhiro Kashige
  • Organizer: World Biotechnology Congress (WBC)
  • Place of Presentation: Boston, USA
  • Year and Date: 2013-06-04
• [Presentation] デキストラン硫酸ナトリウム(DSS)投与により発症するマウス大腸炎の病態に関する性差 (2013)
  • Author(s): 百武美香、田村幸恵、江川さおり、入江圭一、佐藤朝光、平松征洋、上田紗織、福光由起、中島幸彦、三島健一、藤原道弘、鹿志毛信広、見明史雄
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2013-03-28
• [Presentation] Lactobacillus caseiのゲノムDNAに含まれる抗炎症作用を持つオリゴデオキシヌクレオチドの特定と作用機構の解明 (2013)
  • Author(s): 平松征洋、佐藤朝光、入江圭一、椎村翔太、中島幸彦、見明史雄、鹿志毛信広
  • Organizer: 日本農芸化学会2013年度大会
  • Place of Presentation: 東北大学
  • Year and Date: 2013-03-25
• [Presentation] マウスにおけるDSS誘導性大腸炎の病態とTREM- 1/ TREM- 2の発現量比の一致 (2013)
  • Author(s): 江川さおり、百武美香、中村智美、平松征洋、上田紗織、入江圭一、佐藤朝光、中島幸彦、三島健一、鹿志毛信広、見明史雄
  • Organizer: 第86回日本生化学会
  • Place of Presentation: パシフィコ横浜
• [Presentation] Oligodeoxynucleotide5'-TTTTGCCG-3' inhibitsintestinalinflammation (2013)
  • Author(s): Yukihiro Hiramatsu, Tomomitsu Satho, Keiichi Irie, Shota Shiimura, Yukihiko Nakashima, Fumio Miake, Nick Carpino, Nobuhiro Kashige
  • Organizer: World Biotechnology Congress (WBC) 2013
  • Place of Presentation: Boston, USA
• [Presentation] 乳酸菌ゲノムDNA由来の抗炎症作用を持つオリゴデオキシヌクレオチドの特定 (2012)
  • Author(s): 椎村翔太、平松征洋、佐藤朝光、入江圭一、宇高彩奈、上田紗織、中島幸彦、鹿志毛信広、見明史雄
  • Organizer: 第29回日本薬学会九州支部大会
  • Place of Presentation: 熊本大学
  • Year and Date: 2012-12-08
• [Presentation] ヒト結腸癌由来Caco-2細胞における炎症誘発時のProgranulin発現と分泌 (2012)
  • Author(s): 宇高彩奈、平松征洋、佐藤朝光、椎村翔太、入江圭一、古川歩、三島健一、藤原道弘、中島幸彦、鹿志毛信広、見明史雄
  • Organizer: 第29回日本薬学会九州支部大会
  • Place of Presentation: 熊本大学
  • Year and Date: 2012-12-08
• [Presentation] 5種類のLactobacillus属乳酸菌由来ゲノムDNAの抗炎症作用機構に関する研究 (2012)
  • Author(s): 平松征洋、佐藤朝光、入江圭一、椎村翔太、中島幸彦、見明史雄、鹿志毛信広
  • Organizer: 第16回腸内細菌学会
  • Place of Presentation: 神戸市産業振興センター
  • Year and Date: 2012-06-14
• [Presentation] デキストラン硫酸ナトリウム（DSS）投与により発症するマウス大腸炎の病態に関する性差
  • Author(s): 百武美香、田村幸恵、江川さおり、入江圭一、佐藤朝光、平松征洋、上田紗織、福光由起、中島幸彦、三島健一、藤原道弘、鹿志毛信広、見明史雄
  • Organizer: 日本薬学会 第133年会
  • Place of Presentation: パシフィコ横浜
• [Presentation] Lactobacillus caseiのゲノムDNAに含まれる抗炎症作用を持つオリゴデオキシヌクレオチドの特定と作用機構の解明
  • Author(s): 平松征洋、佐藤朝光、入江圭一、椎村翔太、中島幸彦、見明史雄、鹿志毛信広
  • Organizer: 日本農芸化学会 2013年度大会
  • Place of Presentation: 東北大学
• [Presentation] 乳酸菌ゲノムDNA由来の抗炎症作用を持つオリゴデオキシヌクレオチドの特定
  • Author(s): 椎村翔太、平松征洋、佐藤朝光、入江圭一、宇高彩奈、上田紗織、中島幸彦、鹿志毛信広、見明史雄
  • Organizer: 日本農芸化学会 2013年度大会
  • Place of Presentation: 熊本大学
• [Presentation] 5種類のLactobacillus属乳酸菌由来ゲノムDNAの抗炎症作用機構に関する研究
  • Author(s): 平松征洋、佐藤朝光、入江圭一、椎村翔太、中島幸彦、見明史雄、鹿志毛信広
  • Organizer: 第16回腸内細菌学会
  • Place of Presentation: 神戸市産業振興センター「ハーバーホール」
• [Remarks]
  • URL: http://www.pha.fukuoka-u.ac.jp/user/microbiology/web/index.html
• [Remarks] 福岡大学微生物薬品化学研究室
• [Remarks] 福岡大学薬学部微生物薬品化研究室ホームページ
  • URL: http://www.pha.fukuoka-u.ac.jp/user/microbiology/web/