Macrophage migration inhibitory factor is an important mediator in the pathogenesis of gastric inflammation in rats.

Abstract

BACKGROUND & AIMS:

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: X R Huang, C W Chun Hui, Y X Chen, B C Wong, P C Fung, C Metz, C H Cho, W M Hui, R Bucala, S K Lam, H Y Lan, B Chun, Y Wong
• Journal: Gastroenterology (Gastroenterology) Vol. 121 Issue 3 Pg. 619-30 (Sep 2001) ISSN: 0016-5085 [Print] United States
• PMID: 11522746 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Macrophage Migration-Inhibitory Factors
• RNA, Messenger
• Tumor Necrosis Factor-alpha
• Intercellular Adhesion Molecule-1
• Nitric Oxide Synthase
• Nitric Oxide Synthase Type II
• Nos2 protein, rat
• Acetic Acid

Topics

• Acetic Acid
• Acute Disease
• Animals
• Antibodies, Monoclonal (pharmacology)
• Disease Models, Animal
• Gastritis (etiology, immunology, metabolism)
• Gene Expression (immunology)
• In Situ Hybridization
• In Vitro Techniques
• Intercellular Adhesion Molecule-1 (genetics)
• Macrophage Migration-Inhibitory Factors (genetics, immunology, metabolism)
• Macrophages (cytology, enzymology, immunology)
• Male
• Neutrophils (cytology, immunology)
• Nitric Oxide Synthase (genetics)
• Nitric Oxide Synthase Type II
• RNA, Messenger (analysis)
• Rats
• Rats, Sprague-Dawley
• Stomach Ulcer (etiology, immunology, metabolism)
• Tumor Necrosis Factor-alpha (genetics)
• Wound Healing (immunology)