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Interleukin-32γ attenuates ethanol-induced liver injury by the inhibition of cytochrome P450 2E1 expression and inflammatory responses.
- Source :
-
Clinical science (London, England : 1979) [Clin Sci (Lond)] 2015 May 01; Vol. 128 (10), pp. 695-706. - Publication Year :
- 2015
-
Abstract
- Alcohol abuse and alcoholism lead to alcoholic liver disease (ALD), which is a major type of chronic liver disease worldwide. Interleukin-32 (IL-32) is a novel cytokine involved in inflammation and cancer development. However, the role of IL-32 in chronic liver disease has not been reported. In the present paper, we tested the effect of IL-32γ on ethanol-induced liver injury in IL-32γ-overexpressing transgenic mice (IL-32γ mice) after chronic ethanol feeding. Male C57BL/6 and IL-32γ mice (10-12 weeks old) were fed on a Lieber-DeCarli diet containing 6.6% ethanol for 6 weeks. IL-32γ-transfected HepG2 and Huh7 cells, as well as primary hepatocytes from IL-32γ mice, were treated with or without ethanol. The hepatic steatosis and damage induced by ethanol administration were attenuated in IL-32γ mice. Ethanol-induced cytochrome P450 2E1 expression and hydrogen peroxide levels were decreased in the livers of IL-32γ mice, primary hepatocytes from IL-32γ mice and IL-32γ-overexpressing human hepatic cells. The ethanol-induced expression levels of cyclo-oxygenase-2 (COX-2) and IL-6 were reduced in the livers of IL-32γ mice. Because nuclear transcription factor κB (NF-κB) is a key redox transcription factor of inflammatory responses, we examined NF-κB activity. Ethanol-induced NF-κB activities were significantly lower in the livers of IL-32γ mice than in wild-type (WT) mice. Furthermore, reduced infiltration of natural killer cells, cytotoxic T-cells and macrophages in the liver after ethanol administration was observed in IL-32γ mice. These data suggest that IL-32γ prevents ethanol-induced hepatic injury via the inhibition of oxidative damage and inflammatory responses.
- Subjects :
- Alanine Transaminase blood
Animals
Aspartate Aminotransferases blood
Blotting, Western
Cyclooxygenase 2 metabolism
Cytochrome P-450 CYP2E1 Inhibitors therapeutic use
Electrophoretic Mobility Shift Assay
Ethanol administration & dosage
Ethanol adverse effects
Hepatocytes metabolism
Histological Techniques
Humans
Hydrogen Peroxide metabolism
Immunohistochemistry
Interleukin-6 metabolism
Interleukins genetics
Interleukins therapeutic use
Liver metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
NF-kappa B metabolism
Real-Time Polymerase Chain Reaction
Cytochrome P-450 CYP2E1 Inhibitors pharmacology
Gene Expression Regulation, Enzymologic drug effects
Inflammation drug therapy
Interleukins pharmacology
Liver Diseases, Alcoholic drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1470-8736
- Volume :
- 128
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Clinical science (London, England : 1979)
- Publication Type :
- Academic Journal
- Accession number :
- 25583360
- Full Text :
- https://doi.org/10.1042/CS20140576