Macrophage migration inhibitory factor is an important mediator in the pathogenesis of gastric inflammation in rats.
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.
Huang
X R
XR
Department of Medicine, The University of Hong Kong, Hong Kong.
Chun Hui
C W
CW
Chen
Y X
YX
Wong
B C
BC
Fung
P C
PC
Metz
C
C
Cho
C H
CH
Hui
W M
WM
Bucala
R
R
Lam
S K
SK
Lan
H Y
HY
Chun
B
B
Wong
Y
Y
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
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