title: Platelet-activating factor, a critical mediator in the pathogenesis of dextran sulfate sodium-induced colitis in rats.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: Second Department of Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Hirayama
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yokoi
authors.forename: Takanori
authors.initials: T
authors.lastname: Sakaguchi
authors.forename: Toshio
authors.initials: T
authors.lastname: Nakamura
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Kashiwabara
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sunayama
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nakamura
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003092:Colitis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000502:physiology; D010972:Platelet Activating Factor / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D016209:Interleukin-8; D010972:Platelet Activating Factor; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016264:Dextran Sulfate