Lack of macrophage migration inhibitory factor protects mice against concanavalin A-induced liver injury.
BACKGROUND
Macrophage migration inhibitory factor (MIF) is involved in inflammatory and immune-mediated diseases but the role of MIF in liver injury has not yet been elucidated.


METHODS
We investigated biochemically, histologically and immunologically the character of MIF in concanavalin A (Con A)-induced T-cell-mediated liver injury using MIF knockout (KO) mice and wild-type (WT) mice.


RESULTS
MIF KO mice showed significantly decreased serum alanine aminotransferase values and suppressed histological change with massive necrosis of the hepatic parenchymal cells and infiltration of inflammatory cells compared with their WT counterparts. This protection was not mediated by either tumor necrosis factor-alpha or interferon-gamma, which are critical mediators of Con A-induced liver injury, as their serum concentrations were shown to be similar in MIF KO and WT mice. On the other hand, a flow cytometric analysis demonstrated that the number of activated hepatic leukocytes decreased more in the MIF KO mice than in the WT mice.


CONCLUSIONS
A lack of MIF protected the mice from Con A-induced liver injury. Controlling the MIF activity may be a useful therapeutic strategy for treating such T-cell activation-associated liver diseases as autoimmune hepatitis and viral hepatitis.
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
Hiroaki
H
Nakajima
Hitoshi
H
Takagi
Norio
N
Horiguchi
Mitsuo
M
Toyoda
Daisuke
D
Kanda
Toshiyuki
T
Otsuka
Yoshiko
Y
Emoto
Masashi
M
Emoto
Masatomo
M
Mori
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D017252:CD3 Complex / Q000378:metabolism; D003208:Concanavalin A / Q000009:adverse effects*; D004195:Disease Models, Animal; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D037181:Lectins, C-Type; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008934:Mitogens / Q000009:adverse effects*; D009336:Necrosis; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000099192:CD69 Antigens
D000410:Alanine Transaminase; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015415:Biomarkers; D017252:CD3 Complex; D003208:Concanavalin A; D018836:Inflammation Mediators; D007371:Interferon-gamma; D037181:Lectins, C-Type; D008263:Macrophage Migration-Inhibitory Factors; D008934:Mitogens; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000099192:CD69 Antigens