Inhibition of joint inflammation and destruction induced by anti-type II collagen antibody/lipopolysaccharide (LPS)-induced arthritis in mice due to deletion of macrophage migration inhibitory factor (MIF).
OBJECTIVE
Previous studies have demonstrated that neutralization of macrophage migration inhibitory factor (MIF) by anti-MIF antibody decreases joint destruction in the collagen-induced arthritis model. The present study was undertaken to investigate whether selective deletion of MIF inhibits inflammation and joint destruction of the anti-type II collagen antibody (anti-CII Ab)/lipopolysaccharide (LPS)-induced arthritis in mice, in order to determine the role of this cytokine in inflammatory arthritis.


METHODS
Anti-CII Ab/LPS-induced arthritis was induced in MIF-deficient and wild-type mice. The effects of anti-MIF polyclonal antibody administration on anti-CII Ab-induced arthritis were also evaluated.


RESULTS
The expression of MIF protein and mRNA was induced in anti-CII Ab/LPS-induced arthritis joint tissues. Histopathological arthritis scores for synovial inflammation induced by anti-CII Ab/LPS -induced arthritis were significantly decreased in anti-MIF Ab-treated mice and in MIF-deficient mice compared to wild-type mice. In addition, mRNA levels of MMP-13 and MIP-2 in anti-CII Ab/LPS-induced arthritis joint tissues were significantly reduced in MIF-deficient mice compared to wild-type control mice.


CONCLUSIONS
These results indicate that MIF plays a critical role in inflammation and joint destruction in the anti-CII Ab/LPS-induced arthritis model in mice, in part via induction of MMP-13 and neutrophil infiltration through the induction of MIP-2.
Ichiyama
Hiroki
H
Department of Sports Medicine and Joint Reconstruction Surgery, Hokkaido University School of Medicine, Kita-ku Kita-15 Nishi-7, Sapporo 060-8638, Japan.
Onodera
Shin
S
Nishihira
Jun
J
Ishibashi
Teruo
T
Nakayama
Toshinori
T
Minami
Akio
A
Yasuda
Kazunori
K
Tohyama
Harukazu
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D054426:Chemokine CXCL2; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D024043:Collagen Type II / Q000276:immunology*; D017364:Collagenases / Q000235:genetics / Q000378:metabolism; D019746:Intramolecular Oxidoreductases; D008070:Lipopolysaccharides / Q000276:immunology*; D008263:Macrophage Migration-Inhibitory Factors / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D053509:Matrix Metalloproteinase 13; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D013583:Synovial Membrane / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
D000911:Antibodies, Monoclonal; D054426:Chemokine CXCL2; D018925:Chemokines; D024043:Collagen Type II; C404915:Cxcl2 protein, mouse; D008070:Lipopolysaccharides; D008263:Macrophage Migration-Inhibitory Factors; D012333:RNA, Messenger; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse