Investigation of the role of mucosal inductive site and indigenous bacteria on the NSAID-induced enteropathy

• Project/Area Number: 23590941
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Osaka University
• Principal Investigator: IIJIMA Hideki 大阪大学, 医学(系)研究科(研究院), 講師 (90444520)
• Co-Investigator(Kenkyū-buntansha): MASAHIKO Tsujii 大阪大学, 医学系研究科, 准教授 (40303937) ; TSUTOMU Nishida 大阪大学, 医学系研究科, 助教 (20467575) ; SHINICHIRO Shinzaki 大阪大学, 医学系研究科, 助教 (60546860)
• Co-Investigator(Renkei-kenkyūsha): HIROSHI Kiyono 東京大学, 医科学研究所, 教授 (10271032)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 小腸粘膜傷害 / NSAID / 粘膜免疫 / パイエル板 / 樹状細胞 / ＮＳＡＩＤ / 小腸粘膜障害 / ＮＳＡＩＤｓ / CD103陽性樹状細胞 / NSAIDｓ

Research Abstract

We investigated the role of Peyer's patches (PPs) in mouse model of non-steroidal anti-inflammatory drug (NSAID)-induced enteropathy. We found PP-null mice showed greater indomethacin-induced enteropathy than the wild type mice. The proportion of CD103+ DCs and IL-10 expressing CD4+ T cells of PPs increased after indomethacin treatment. Protective effect was not associated with commensal bacteria. These results indicate that PPs play a protective role in NSAID-induced enteropathy, and this protection is associated with an increase in CD103+ DCs and IL-10 producing CD4+ T cells in the intestine. PPs are considered to be a target for digestive inflammatory diseases.

Research Products

• [Journal Article] Peyer's patches play a protective role in nonsteroidal anti-inflammatory drug-induced enteropathy in mice. (2014)
  • Author(s): Hiyama S, Iijima H, Shinzaki S, Inoue T, Shiraishi E, Kawai S, Araki M, Kato M, Hayashi Y, Nishida T, Fujii H, Mukai A, Shibata N, Sato S, Kiyono H, Gotoh K, Motooka D, Nakamura S, Iida T, Tsujii M, Takehara T.
  • Journal Title: Inflamm Bowel Dis. Volume: 5 Issue: 5 Pages: 790-9
  • DOI: 10.1097/mib.0000000000000017
  • Peer Reviewed / Open Access
• [Journal Article] Narrow Band Imaging with Magnifying Endoscopy for Peyer's Patches in Patients with Inflammatory Bowel Disease (2013)
  • Author(s): Hiyama S, Iijima H, Shinzaki S, Mukai A, Inoue T, Shiraishi E, Kawai S, Yamada T, Nishida T, Tsujii M, Takehara T
  • Journal Title: Digestion Volume: 87(4) Pages: 269-80
• [Journal Article] Lectin-based Immunoassay for Aberrant IgG Glycosylation as the Biomarker for Crohn's Disease (2013)
  • Author(s): Shinzaki S, Kuroki E, Iijima H, Tatsunaka N, Ishii M, Fujii H, Kamada Y, Kobayashi T, Shibukawa N, Inoue T, Tsujii M, Takeishi S, Mizushima T, Ogata A, Naka T, Plevy SE, Takehara T, Miyoshi E
  • Journal Title: Inflamm Bowel Dis Volume: 19(2) Pages: 321-31
• [Journal Article] CagA mediates epigenetic regulation to attenuate let-7 expression in Helicobacter pylori-related carcinogenesis (2013)
  • Author(s): Hayashi Y, Tsujii M, Wang J, Kondo J, Akasaka T, Jin Y, Li W, Nakamura T, Nishida T, Iijima H, Tsuji S, Kawano S, Hayashi N, Takehara T
  • Journal Title: Gut Volume: 62(11) Pages: 1536-46
• [Journal Article] Amelioration of Small Bowel Injury by Switching from Nonselective Nonsteroidal Anti-Inflammatory Drugs to Celecoxib in Rheumatoid Arthritis Patients: A Pilot Study (2013)
  • Author(s): Inoue, T., Iijima, H., Arimitsu, J., Hagihara, K., Kawai, S., Shiraishi, E., Hiyama, S., Mukai, A., Shinzaki, S., Nishida, T., Ogata, A., Tsujii, M., Takehara, T.
  • Journal Title: Digestion Volume: 89 Issue: 2 Pages: 124-132
  • DOI: 10.1159/000357229
  • Peer Reviewed
• [Journal Article] Narrow Band Imaging with Magnifying Endoscopy for Peyer's Patches in Patients with Inflammatory Bowel Disease (2013)
  • Author(s): Hiyama, S., Iijima, H., Shinzaki, S., Mukai, A., Inoue, T., Shiraishi, E., Kawai, S., Yamada, T., Nishida, T., Tsujii, M., Takehara, T.
  • Journal Title: Digestion Volume: 87 Issue: 4 Pages: 269-80
  • DOI: 10.1159/000349953
  • Peer Reviewed
• [Journal Article] Lectin-based immunoassay for aberrant IgG glycosylation as the biomarker for Crohn's disease. (2013)
  • Author(s): Shinzaki S, 他13名, Naka T, Plevy S E, Takehara T, Miyoshi E.
  • Journal Title: Inflamm Bowel Dis. Volume: 19（2） Issue: 2 Pages: 321-31
  • DOI: 10.1097/mib.0b013e318280eade
  • Peer Reviewed
• [Journal Article] Narrow Band Imaging with Magnifying Endoscopy for Peyer’s Patches in Patients with Inflammatory Bowel Disease (2013)
  • Author(s): S. Hiyama, H. Iijima, S. Shinzaki, A. Mukai, T. Inoue, Eri Shiraishi, S. Kawai, T. Yamada, T. Nishida, M. Tsujii and T. Takehara
  • Journal Title: Digestion Volume: -
  • Peer Reviewed
• [Journal Article] Serum leucine-rich alpha-2 glycoprotein is a disease activity biomarker in ulcerative colitis (2012)
  • Author(s): Serada S, Fujimoto M, Terabe F, Iijima H, Shinzaki S, Matsuzaki S, Ohkawara T, Nezu R, Nakajima S, Kobayashi T, Plevy SE, Takehara T, Naka T
  • Journal Title: Inflamm Bowel Dis Volume: 18(11) Pages: 2169-79
• [Journal Article] Extracellular ATP mediates mast cell-dependent intestinal inflammation through P2X7 purinoceptors (2012)
  • Author(s): Kurashima Y, Amiya T, Nochi T, Fujisawa K, Haraguchi T, Iba H, Tsutsui H, Sato S, Nakajima S, Iijima H, Kubo M, Kunisawa J, Kiyono H
  • Journal Title: Nat Commun Volume: 3 Pages: 1034-1034
• [Journal Article] Quantitative change of IgA hinge O-glycan composition is a novel marker of therapeutic responses of IgA nephropathy (2012)
  • Author(s): Iwatani H, Inoue T, Wada Y, Nagasawa Y, Yamamoto R, Iijima H, Takehara T, Imai E, Rakugi H, Isaka Y
  • Journal Title: Biochem Biophys Res Commun Volume: 428(3) Pages: 339-42
• [Journal Article] Deficiency of N-acetylgalactosamine in O-linked oligosaccharides of IgA is a novel biologic marker for Crohn's disease (2012)
  • Author(s): Inoue T, Iijima H, Tajiri M, Shinzaki S, Shiraishi E, Hiyama S, Mukai A, Nakajima S, Iwatani H, Nishida T, Mizushima T, Yasui T, Isaka Y, Kanto T, Tsujii M, Miyoshi E, Wada Y, Takehara T
  • Journal Title: Inflamm Bowel Dis Volume: 18(9) Pages: 1723-34
• [Journal Article] Functional analysis of agalactosyl IgG in inflammatory bowel disease patients (2011)
  • Author(s): Nakajima, S., H. Iijima, S. Shinzaki, S. Egawa, T. Inoue, A. Mukai, Y. Hayashi, J. Kondo, T. Akasaka, T. Nishida, T. Kanto, E. Morii, T. Mizushima, E. Miyoshi, M. Tsujii, N. Hayashi
  • Journal Title: Inflamm Bowel Dis Volume: 17 Pages: 927-936
  • NAID: 10028268520
• [Journal Article] Comparative analysis of the effects of anti-IL-6 receptor mAb and anti-TNF mAb treatment on CD4(+) T-cell responses in murine colitis (2011)
  • Author(s): Terabe, F., M. Fujimoto, S. Serada, S. Shinzaki, H. Iijima, M. Tsujii, N. Hayashi, S. Nomura, H. Kawahata, M.H. Jang, M. Miyasaka, M. Mihara, Y. Ohsugi, T. Kishimoto, and T. Naka
  • Journal Title: Inflamm Bowel Dis Volume: 17 Pages: 491-502
• [Journal Article] COX-2選択的阻害薬によるNSAID起因性小腸粘膜傷害の治療・予防 (2011)
  • Author(s): 井上隆弘、 飯島英樹、 白石衣里、 日山智史、 他
  • Journal Title: 消化器内科 Volume: 53 Pages: 29-34
• [Journal Article] Peyer's patches play a protective role in non-steroidal anti-inflammatory drug-induced enteropathy in mice
  • Author(s): Hiyama S, Iijima H, Shinzaki S, Inoue T, Shiraishi E, Kawai S, Araki M, Kato M, Hayashi Y, Nishida T, Fujii H, Mukai A, Shibata N, Sato S, Kiyono H, Gotoh K, Motooka D, Nakamura S, Iida T, Tsujii M, Takehara T
  • Journal Title: Inflamm Bowel Dis Volume: (In press)
• [Journal Article] Regulation of anergy-related ubiquitin E3 ligase, GRAIL, in murine models of colitis and patients with Crohn's disease
  • Author(s): Mukai A, Iijima H, Hiyama S, Fujii H, Shinzaki S, Inoue T, Shiraishi E, Kawai S, Araki M, Hayashi Y, Kondo J, Mizushima T, Kanto T, Egawa S, Nishida T, Tsujii M, Takehara T
  • Journal Title: J Gastroenterol Volume: (In press)
• [Presentation] Observation of Peyer's patch using narrow band imaging with magnifying endoscopy is useful in predicting the recurrence in ulcerative colitis patients (2013)
  • Author(s): Hiyama, S., H. Iijima, S. Shinzaki, T. Inoue, E. Shiraishi, S. Kawai, M. Araki, T. Nishida, M. Tsujii, and T. Takehara
  • Organizer: UEGW
  • Place of Presentation: Berlin, Germany
• [Presentation] Peyer's Patches Play a Protective Role in NSAIDs-Induced Enteropathy (2013)
  • Author(s): Hiyama, S., H. Iijima, S. Kawai, E. Shiraishi, A. Mukai, T. Inoue, S. Shinzaki, M. Tsujii, and T. Takehara
  • Organizer: DDW
  • Place of Presentation: Orland
• [Presentation] Peyer's patches play a protective role in NSAIDs-induced small bowel injury (2013)
  • Author(s): Hiyama, S., Iijima, H., Shinzaki, S., Shibata, N., Sato S., Tsujii, M., Kiyono, H., Takehara, T
  • Organizer: 第42回日本免疫学会
  • Place of Presentation: 幕張メッセ
• [Presentation] Observation of Peyer's patch using narrow band imaging with magnifying endoscopy is useful in predicting the recurrence in ulceratie colitis patients (2013)
  • Author(s): Hiyama, S., H. Iijima, S. Kawai, E. Shiraishi, A. Mukai, T. Inoue, S. Shinzaki, M. Tsujii, and T. Takehara.
  • Organizer: UEGW
  • Place of Presentation: Berlin, Germany
• [Presentation] Peyer's Patches Play a Protective Role in NSAIDs-Induced Enteropathy (2013)
  • Author(s): Hiyama, S., H. Iijima, S. Shinzaki, T. Inoue, E. Shiraishi, S. Kawai, M. Araki, T. Nishida, M. Tsujii, and T. Takehara.
  • Organizer: DDW
  • Place of Presentation: Orland, USA
• [Presentation] 関節リウマチ患者におけるNSAIDs小腸粘膜傷害に対するメサラジンの有用性および粘膜傷害のリスク因子に関する検討 (2013)
  • Author(s): 井上隆弘, 飯島英樹, 有光潤介, 萩原圭祐, 川井翔一朗, 白石衣里, 日山智史, 向井章, 新崎信一郎, 西田勉, 緒方篤, 辻井正彦, 竹原徹郎
  • Organizer: JDDW2013
  • Place of Presentation: グランドプリンスホテル新高輪
• [Presentation] Alteration of Peyer's patch in patients with inflammatory bowel disease observed in using narrow band imaging with magnifying endoscopy (2012)
  • Author(s): Hiyama, S., H. Iijima, S. Shinzaki, A. Mukai, T. Inoue, S. Kawai, E. Shiraishi, T. Yamada, T. Nishida, M. Tsujii, and T. Takehara
  • Organizer: UEGW
  • Place of Presentation: Amsterdam, Netherland
• [Presentation] Efficacy of balloon dilation using double-balloon enteroscopy for small-bowel strictures in patients with symptomatic Crohn's disease (2012)
  • Author(s): Inoue, T., H. Iijima, and T. Takehara
  • Organizer: ASIBD 2012
  • Place of Presentation: Seoul, Korea
• [Presentation] Narrow Band Imaging With Magnifying Endoscopy for Peyer's Patches in Patients With Inflammatory Bowel Disease (2012)
  • Author(s): Hiyama, S., H. Iijima, S. Shinzaki, A. Mukai, S. Nakajima, T. Inoue, E. Shiraishi, T. Yamada, T. Nishida, M. Tsujii, and T. Takehara
  • Organizer: DDW 2012
  • Place of Presentation: San Diego
• [Presentation] Efficacy of balloon dilation using double-balloon enteroscopy for small-bowel strictures in patients with symptomatic Crohn's disease (2012)
  • Author(s): Inoue, T., H. Iijima, S. Yamaguchi, S. Egawa, Y. Arimoto, K. Tominaga, A. Maekawa, S. Hiyama, S. Shinzaki, M. Komori, T. Nishida, H. Hagiwara, M. Oshita, M. Tsujii, M. Kubo, and T. Takehara
  • Organizer: UEGW
  • Place of Presentation: Amsterdam, Netherland
• [Presentation] パイエル板はNSAIDs起因性小腸粘膜傷害に保護的に働く (2012)
  • Author(s): 日山智史, 飯島英樹, 白石衣里, 向井章, 井上隆弘, 中島佐知子, 新﨑信一郎, 辻井正彦, 竹原徹郎
  • Organizer: JDDW2012(消化器病学会)
  • Place of Presentation: 神戸
• [Presentation] ALTERNATION OF PEYER’S PATCH IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE: OBSERVATION USING NARROW BAND IMAGING WITH MAGNIFYING ENDOSCOPY. (2012)
  • Author(s): Satoshi Hiyama,Hideki Iijima,Shinichiro Shinzaki,Akira Mukai,Takahiro Inoue,Syouichirou Kawai,Eri Shiraishi,Takuya Yamada,Tsutomu Nishida,Masahiko Tsujii,Tetsuo Takehara
  • Organizer: United European Gastroenterology: UEG Week 2012
  • Place of Presentation: Amsterdam, Netherland
• [Presentation] NSAID起因性小腸粘膜障害に対するバイエル板の関与 (2011)
  • Author(s): 日山智史, 飯島英樹, 竹原徹郎
  • Organizer: 第53回日本消化器病学会大会
  • Place of Presentation: 福岡
• [Presentation] Narrow Band Imaging With Magnifying Endoscopy for Peyer's Patches in Patients With Inflammatory Bowel Disease
  • Author(s): Satoshi Hiyama, Hideki Iijima, Shinichiro Shinzaki, Akira Mukai, Sachiko Nakajima, Takahiro Inoue, Eri Shiraishi, Takuya Yamada, Tsutomu Nishida, Masahiko Tsujii,Tetsuo Takehara
  • Organizer: Digestive Disease Week 2012
  • Place of Presentation: San Diego, USA
• [Presentation] IBD患者におけるパイエル板NBI拡大観察
  • Author(s): 日山智史、飯島英樹、川井翔一郎、白石衣里、向井章、井上隆弘、新崎信一郎、辻井正彦、竹原徹郎
  • Organizer: 第50回小腸研究会
  • Place of Presentation: 京都
• [Presentation] パイエル板はNSAIDs起因性小腸粘膜傷害に保護的に働く
  • Author(s): 日山智史、飯島英樹、白石衣里、向井章、井上隆弘、中島佐知子、新﨑信一郎、辻井正彦、竹原徹郎
  • Organizer: JDDW2012(消化器病学会）
  • Place of Presentation: 神戸
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/pub/gh/index.html