Macrophage migration inhibitory factor contributes to the development of acute dextran sulphate sodium-induced colitis in Toll-like receptor 4 knockout mice.
Toll-like receptor 4 (TLR4), which recognizes lipopolysaccharides, plays an important role in the innate immune response. In this study, we investigated the role of TLR4 in the development of experimental colitis with regard to the biological actions of macrophage migration inhibitory factor (MIF) using TLR4 null ((-/-)) mice. TLR4(-/-) mice were given 2% dextran sulphate sodium (DSS) in drinking water to induce colitis, which was clinically and histologically as severe as that seen in wild-type (WT) mice. The level of tumour necrosis factor (TNF)-alpha in colon tissues was increased in WT mice but unchanged in TLR4(-/-) mice. The level of myeloperoxidase (MPO) activity in colon tissues was increased by DSS administration in both TLR4(-/-) and WT mice. The expression of MIF was up-regulated in the colons of TLR4(-/-) mice with acute DSS-induced colitis. An anti-MIF antibody significantly suppressed colitis and elevation of matrix metalloproteinase-13 in TLR4(-/-) mice. The current results obtained from TLR4(-/-) mice provide evidence that MIF plays a critical role in the development of acute DSS-induced colitis.
Ohkawara
T
T
Department of Gastroenterology and Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. tokawara@med.hokudai.ac.jp
Takeda
H
H
Nishihira
J
J
Miyashita
K
K
Nihiwaki
M
M
Ishiguro
Y
Y
Takeda
K
K
Akira
S
S
Iwanaga
T
T
Sugiyama
T
T
Asaka
M
M
D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D015153:Blotting, Western / Q000379:methods; D003093:Colitis, Ulcerative / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D003106:Colon / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D016264:Dextran Sulfate; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry / Q000379:methods; D008263:Macrophage Migration-Inhibitory Factors / Q000032:analysis / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009195:Peroxidase / Q000032:analysis; D011971:Receptors, Immunologic / Q000235:genetics*; D015398:Signal Transduction / Q000502:physiology*; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000911:Antibodies, Monoclonal; D008263:Macrophage Migration-Inhibitory Factors; D011971:Receptors, Immunologic; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D016264:Dextran Sulfate; D009195:Peroxidase