Platelet-activating factor, a critical mediator in the pathogenesis of dextran sulfate sodium-induced colitis in rats.

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.

• Authors: Kazuhisa Hirayama, Yoshihiro Yokoi, Takanori Sakaguchi, Toshio Nakamura, Hidefumi Kashiwabara, Kenichi Sunayama, Satoshi Nakamura
• Journal: Diseases of the colon and rectum (Dis Colon Rectum) Vol. 46 Issue 1 Pg. 100-10 (Jan 2003) ISSN: 0012-3706 [Print] United States
• PMID: 12544529 (Publication Type: Journal Article)

Chemical References

• Cytokines
• Interleukin-8
• Platelet Activating Factor
• RNA, Messenger
• Tumor Necrosis Factor-alpha
• Dextran Sulfate

Topics

• Analysis of Variance
• Animals
• Colitis (metabolism, pathology, prevention & control)
• Cytokines (metabolism)
• Dextran Sulfate
• Disease Models, Animal
• Interleukin-8 (metabolism)
• Male
• Neutrophils (physiology)
• Platelet Activating Factor (metabolism)
• RNA, Messenger (metabolism)
• Rats
• Rats, Wistar
• Statistics, Nonparametric
• Tumor Necrosis Factor-alpha (metabolism)
• Up-Regulation