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Transgenic over-expression of macrophage migration inhibitory factor renders mice markedly more susceptible to experimental colitis.
- Source :
-
Clinical and experimental immunology [Clin Exp Immunol] 2005 May; Vol. 140 (2), pp. 241-8. - Publication Year :
- 2005
-
Abstract
- Enhanced production of macrophage migration inhibitory factor (MIF) is recognized in patients with inflammatory bowel disease (IBD) and mice with experimental colitis; however, the precise molecular function of MIF in colitis is not fully understood. To further investigate this matter, we examined the pathological features of MIF transgenic mice with dextran sulphate sodium (DSS)-induced colitis. We generated transgenic mice carrying a murine MIF cDNA driven by a cytomegalovirus enhancer and a beta-actin/beta-globin promoter. Mice were orally administered 1-4% DSS in drinking water for 7 days. Clinical disease activity, survival and histological features were evaluated. The level of myeloperoxidase (MPO) activity in the colon tissue was measured to assess neutrophil infiltration. The level of corticosterone in the serum was measured by enzyme linked-immunosorbent assay (ELISA). MIF mRNA and protein were markedly up-regulated in the colon and serum obtained from MIF transgenic mice. The severity of the colitis induced by 1% DSS treatment was markedly higher in MIF transgenic mice than in wild-type mice. We also found that MPO activity was significantly higher in MIF transgenic mice than wild-type mice in response to DSS stimulation. Interestingly, the corticosterone level remained unchanged in MIF transgenic mice. MIF enhances DSS-induced colitis, in part via neutrophil accumulation and inhibition of glucocorticoid bioactivity.
- Subjects :
- Animals
Colitis chemically induced
Colitis pathology
Colon metabolism
Corticosterone blood
Dextran Sulfate
Disease Susceptibility
Macrophage Migration-Inhibitory Factors biosynthesis
Macrophage Migration-Inhibitory Factors genetics
Mice
Mice, Inbred C57BL
Mice, Inbred ICR
Mice, Transgenic
Neutrophil Infiltration
Peroxidase metabolism
RNA, Messenger genetics
Severity of Illness Index
Colitis metabolism
Macrophage Migration-Inhibitory Factors physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0009-9104
- Volume :
- 140
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Clinical and experimental immunology
- Publication Type :
- Academic Journal
- Accession number :
- 15807847
- Full Text :
- https://doi.org/10.1111/j.1365-2249.2005.02771.x