Macrophage migration inhibitory factor contributes to ethanol-induced liver injury by mediating cell injury, steatohepatitis, and steatosis.
Hepatology
; 57(5): 1980-91, 2013 May.
Article
in En
| MEDLINE
| ID: mdl-23174952
ABSTRACT
UNLABELLED Macrophage migration inhibitory factor (MIF), a multipotent protein that exhibits both cytokine and chemotactic properties, is expressed by many cell types, including hepatocytes and nonparenchymal cells. We hypothesized that MIF is a key contributor to liver injury after ethanol exposure. Female C57BL/6 or MIF-/- mice were fed an ethanol-containing liquid diet or pair-fed control diet for 4 (11% total kcal;early response) or 25 (32% kcal; chronic response) days. Expression of MIF messenger RNA (mRNA) was induced at both 4 days and 25 days of ethanol feeding. After chronic ethanol, hepatic triglycerides and plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were increased in wildtype, but not MIF-/-, mice. In order to understand the role of MIF in chronic ethanol-induced liver injury, we investigated the early response of wildtype and MIF-/- to ethanol. Ethanol feeding for 4 days increased apoptosis of hepatic macrophages and activated complement in both wildtype and MIF-/- mice. However, tumor necrosis factor alpha (TNF-α) expression was increased only in wildtype mice. This attenuation of TNF-α expression was associated with fewer F4/80+ macrophages in liver of MIF-/- mice. After 25 days of ethanol feeding, chemokine expression was increased in wildtype mice, but not MIF-/- mice. Again, this protection was associated with decreased F4/80+ cells in MIF-/- mice after ethanol feeding. Chronic ethanol feeding also sensitized wildtype, but not MIF-/-, mice to lipopolysaccharide, increasing chemokine expression and monocyte recruitment into the liver. CONCLUSION:
Taken together, these data indicate that MIF is an important mediator in the regulation of chemokine production and immune cell infiltration in the liver during ethanol feeding and promotes ethanol-induced steatosis and hepatocyte damage.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Macrophage Migration-Inhibitory Factors
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Intramolecular Oxidoreductases
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Ethanol
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Fatty Liver
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Chemical and Drug Induced Liver Injury
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Liver
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Hepatology
Year:
2013
Document type:
Article
Affiliation country:
Estados Unidos
Publication country:
EEUU
/
ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
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USA