title: Macrophage migration inhibitory factor is an important mediator in the pathogenesis of gastric inflammation in rats.
abstract: OBJECTIVE
  Macrophage migration inhibitory factor (MIF) has been shown to play a pivotal role in inflammatory and immune-mediated diseases. This study investigates the role of MIF in gastric inflammation.
  
  
  METHODS
  Expression of MIF was examined in a rat gastric ulcer model induced by acetic acid, and the functional role of MIF in acute gastric ulcer was investigated by administration of a neutralizing anti-MIF antibody.
  
  
  RESULTS
  MIF messenger RNA and protein were markedly up-regulated in acute gastric ulcer, which correlated with the accumulation of macrophages (P < 0.001) and neutrophils (P < 0.05) at the site of inflammation. Macrophages, like neutrophils, were the major inflammatory cells infiltrating the ulcer base and they strongly expressed inducible nitric oxide synthase. However, macrophages, not neutrophils, were a rich source of MIF production in acute gastric ulcer. In vivo and in vitro blockade of MIF with the neutralizing anti-MIF antibody significantly inhibited the marked up-regulation of MIF, tumor necrosis factor alpha, inducible nitric oxide synthase, and intercellular adhesion molecule-1. This was associated with the marked inhibition of macrophage (70% reduced) and neutrophil (60% reduced) accumulation and activation, thus reducing ulcer sizes and attenuating ulceration.
  
  
  CONCLUSIONS
  This study has shown that MIF was markedly up-regulated during acute gastric ulcer. Inhibition of acute gastric ulcer by blockade of MIF indicates that MIF is a key inflammatory mediator and plays a pathogenic role in gastric inflammation.
authors.affiliation: Department of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: X R
authors.initials: XR
authors.lastname: Huang
authors.forename: C W
authors.initials: CW
authors.lastname: Chun Hui
authors.forename: Y X
authors.initials: YX
authors.lastname: Chen
authors.forename: B C
authors.initials: BC
authors.lastname: Wong
authors.forename: P C
authors.initials: PC
authors.lastname: Fung
authors.forename: C
authors.initials: C
authors.lastname: Metz
authors.forename: C H
authors.initials: CH
authors.lastname: Cho
authors.forename: W M
authors.initials: WM
authors.lastname: Hui
authors.forename: R
authors.initials: R
authors.lastname: Bucala
authors.forename: S K
authors.initials: SK
authors.lastname: Lam
authors.forename: H Y
authors.initials: HY
authors.lastname: Lan
authors.forename: B
authors.initials: B
authors.lastname: Chun
authors.forename: Y
authors.initials: Y
authors.lastname: Wong
mesh_terms: D019342:Acetic Acid; D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D004195:Disease Models, Animal; D005756:Gastritis / Q000209:etiology* / Q000276:immunology* / Q000378:metabolism; D015870:Gene Expression / Q000276:immunology; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D008297:Male; D009504:Neutrophils / Q000166:cytology / Q000276:immunology; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000209:etiology* / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014945:Wound Healing / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D008263:Macrophage Migration-Inhibitory Factors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D019342:Acetic Acid