Lack of macrophage migration inhibitory factor suppresses innate immune response in murine dextran sulfate sodium-induced colitis.
OBJECTIVE
Macrophage migration inhibitory factor (MIF) plays an important role in the development of inflammatory diseases. Recent studies have indicated an association of MIF with gastrointestinal inflammation including colitis, but the mechanism by which MIF exacerbates gut inflammation has not been fully clarified. In this study, in order further to clarify the role of MIF in intestinal inflammation, we investigated the association of MIF with innate immunity in experimental colitis using MIF-deficient mice.


METHODS
Colitis was induced by treating mice with 3% dextran sulfate sodium (DSS) solution for 7 days. The expressions of chemokines in the colon were determined by reverse transcriptase-polymerase chain reaction (RT-PCR). Myeloperoxidase activity in the colon was measured and immunohistochemistry for F4/80 was analyzed.


RESULTS
DSS treatment increased the level of myeloperoxidase activity and infiltration of F4/80-stained cells in the colon, and up-regulated the mRNA expressions in macrophage inflammatory protein (MIP)-1alpha, MIP-2, macrophage chemotaxic protein (MCP)-1, and interferon inducible protein (IP)-10 in wild-type mice. In contrast, this increase and up-regulation were not observed in the colon of MIF-deficient mice treated with DSS.


CONCLUSIONS
Our findings indicate that a lack of MIF suppresses the innate immune response in DSS-induced colitis.
Ohkawara
Tatsuya
T
Department of Medical Management and Informatics, Faculty of Business Administration and Information Science, Hokkaido Information University, Nishinopporo, Japan. tatsuyaohkawara@umin.ac.jp
Mitsuyama
Keiichi
K
Takeda
Hiroshi
H
Asaka
Masahiro
M
Fujiyama
Yoshihide
Y
Nishihira
Jun
J
D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism*; D016264:Dextran Sulfate / Q000009:adverse effects; D007113:Immunity, Innate; D019746:Intramolecular Oxidoreductases / Q000276:immunology*; D008263:Macrophage Migration-Inhibitory Factors / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D020133:Reverse Transcriptase Polymerase Chain Reaction
D008263:Macrophage Migration-Inhibitory Factors; D016264:Dextran Sulfate; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse