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Platelet-Activating Factor, a Critical Mediator in the Pathogenesis of Dextran Sulfate Sodium-Induced Colitis in Rats

  • Published:
Diseases of the Colon & Rectum

Abstract

PURPOSE: Disorder of mucosal immunity based on an imbalance between proinflammatory and anti-inflammatory cytokines is believed to be a major factor in the pathogenesis of ulcerative colitis. Platelet-activating factor potentially stimulates the production of proinflammatory cytokines and recruits inflammatory cells. The aim of this study was to determine whether and to what extent platelet-activating factor plays a role in the pathogenesis of ulcerative colitis. METHODS: Using dextran sulfate sodium-induced colitis in rats as a model of ulcerative colitis, we analyzed the composition of cellular infiltrates and the local tissue expression of messenger ribonucleic acid for cytokine-induced neutrophil chemoattractant and tumor necrosis factor-alpha. To directly assess the impact of platelet-activating factor on the development of colitis, we also determined the efficacy of a specific platelet-activating factor receptor antagonist for preventing dextran sulfate sodium-induced colitis. RESULTS: The activity of colitis was well correlated with the upregulation of cytokine-induced neutrophil chemoattractant and tumor necrosis factor-alpha messenger ribonucleic acid in local tissues and infiltration of cytokine-induced neutrophil chemoattractant-positive neutrophils and ED1-positive macrophages. The platelet-activating factor receptor antagonist effectively ameliorated colitis, along with causing a decrease in the tissue cytokine-induced neutrophil chemoattractant messenger ribonucleic acid level and a decline in neutrophil and macrophage infiltration. However, the antagonist did not alter tissue levels of tumor necrosis factor-alpha messenger ribonucleic acid. CONCLUSION: Platelet-activating factor plays a critical role in the pathogenesis of dextran sulfate sodium-induced colitis through recruitment of cytokine-induced neutrophil chemoattractant-positive neutrophils and macrophages and/or stimulation of cytokine-induced neutrophil chemoattractant release from activated neutrophils. The tissue level of tumor necrosis factor-alpha messenger ribonucleic acid does not closely reflect the activity of colitis.

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    Authors
    1. Kazuhisa Hirayama M.D.
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    2. Yoshihiro Yokoi M.D.
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    3. Takanori Sakaguchi M.D.
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    4. Toshio Nakamura M.D.
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    5. Hidefumi Kashiwabara M.D.
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    6. Kenichi Sunayama M.D.
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    7. Satoshi Nakamura M.D.
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    Hirayama, K., Yokoi, Y., Sakaguchi, T. et al. Platelet-Activating Factor, a Critical Mediator in the Pathogenesis of Dextran Sulfate Sodium-Induced Colitis in Rats. Dis Colon Rectum 46, 100–110 (2003). https://doi.org/10.1007/s10350-004-6503-7

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    • DOI: https://doi.org/10.1007/s10350-004-6503-7

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