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Research ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

An Oral Drug Delivery System Targeting Immune-Regulating Cells Ameliorates Mucosal Injury in Trinitrobenzene Sulfonic Acid-Induced Colitis

Hiroshi Nakase, Kazuichi Okazaki, Yasuhiko Tabata, Suguru Uose, Masaya Ohana, Kazushige Uchida, Toshiki Nishi, Andra's Debreceni, Toshiyuki Itoh, Chiharu Kawanami, Masao Iwano, Yoshito Ikada and Tsutomu Chiba
Journal of Pharmacology and Experimental Therapeutics June 2001, 297 (3) 1122-1128;
Hiroshi Nakase
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Kazuichi Okazaki
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Yasuhiko Tabata
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Suguru Uose
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Masaya Ohana
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Kazushige Uchida
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Toshiki Nishi
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Andra's Debreceni
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Toshiyuki Itoh
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Chiharu Kawanami
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Masao Iwano
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Yoshito Ikada
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Tsutomu Chiba
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Abstract

Control of immune-regulating cells in the colonic mucosa is important in the treatment of patients with inflammatory bowel disease (IBD). The aim of study was to examine the therapeutic effect of dexamethasone (DX) microspheres on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats, a model for human Crohn's disease. DX microspheres and DX alone were administered orally to rats with TNBS-induced colitis. The macroscopic score, histological score, myeloperoxidase (MPO) activity, nitric oxide (NO) production, and gene expressions of proinflammatory cytokines, cyclooxygenase (COX)-1, and COX-2 in the colonic tissue were determined. Proliferating cell nuclear antigen (PCNA) staining and expression of nuclear transcription factor (NF)-κB in colonic tissues were also investigated. Macroscopic score, histological score, MPO activity, and NO production in rats treated with DX microspheres were significantly lower than in those treated with DX alone. The gene expression of proinflammatory cytokines and COX-2 in rats treated with DX microspheres was down-regulated, compared with that in rats treated with DX alone. The number of PCNA-positive cells in the DX microsphere group was larger than in the group treated with DX alone. DX microspheres suppressed NF-κB activation in TNBS-induced colitis more strongly than DX alone. Oral administration of DX microspheres appears to ameliorate mucosal injury in TNBS-induced colitis. This drug delivery system could be an ideal therapy for human IBD.

Footnotes

  • Send reprint requests to: Dr. Kazuichi Okazaki, Division of Gastroenterology and Endoscopic Medicine, Graduate School of Kyoto University, 54 Shogoinkawara-cho, Sakyoku, Kyoto, 606-8507, Japan. E-mail:okak{at}kuhp.kyoto-u.ac.jp

  • This work was supported by Grant-in-aid for Scientific Research 09670543 from the Ministry of Culture and Science of Japan, by Grant-in-aid for Research for the Future Program JSPS-RFTF 97100201 from the Japan Society for the Promotion of Science, by Research Fellowship 03340 from the Japan Society for the Promotion of Science for Young Scientists, and by supporting research funds JFE-1997 from the Japanese Foundation for Research and Promotion of Endoscopy.

  • Abbreviations:
    UC
    ulcerative colitis
    CD
    Crohn's disease
    IBD
    inflammatory bowel disease
    PDLLA
    poly-d,l-lactic acid
    DX
    dexamethasone
    DSS
    dextran sulfate sodium
    TNBS
    2,4,6-trinitrobenzene sulfonic acid
    IFN
    interferon
    IL
    interleukin
    NF-κB
    nuclear factor-κB
    MPO
    myeloperoxidase
    NO
    nitric oxide
    COX
    cyclooxygenase
    PBS
    phosphate-buffered saline
    PCNA
    proliferating cell nuclear antigen
    RT
    reverse transcription
    PCR
    polymerase chain reaction
    TNF
    tumor necrosis factor
    EMSA
    electrophoretic mobility shift assays
    • Received September 9, 2000.
    • Accepted February 21, 2001.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 297 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 297, Issue 3
1 Jun 2001
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Research ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

An Oral Drug Delivery System Targeting Immune-Regulating Cells Ameliorates Mucosal Injury in Trinitrobenzene Sulfonic Acid-Induced Colitis

Hiroshi Nakase, Kazuichi Okazaki, Yasuhiko Tabata, Suguru Uose, Masaya Ohana, Kazushige Uchida, Toshiki Nishi, Andra's Debreceni, Toshiyuki Itoh, Chiharu Kawanami, Masao Iwano, Yoshito Ikada and Tsutomu Chiba
Journal of Pharmacology and Experimental Therapeutics June 1, 2001, 297 (3) 1122-1128;

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Research ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

An Oral Drug Delivery System Targeting Immune-Regulating Cells Ameliorates Mucosal Injury in Trinitrobenzene Sulfonic Acid-Induced Colitis

Hiroshi Nakase, Kazuichi Okazaki, Yasuhiko Tabata, Suguru Uose, Masaya Ohana, Kazushige Uchida, Toshiki Nishi, Andra's Debreceni, Toshiyuki Itoh, Chiharu Kawanami, Masao Iwano, Yoshito Ikada and Tsutomu Chiba
Journal of Pharmacology and Experimental Therapeutics June 1, 2001, 297 (3) 1122-1128;
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