Interleukin-32γ attenuates ethanol-induced liver injury by the inhibition of cytochrome P450 2E1 expression and inflammatory responses.

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.

• Authors: Dong Hun Lee, Dae Hwan Kim, Chul Ju Hwang, Sukgil Song, Sang Bae Han, Youngsoo Kim, Hwan Soo Yoo, Young Suk Jung, Soo Hyun Kim, Do Young Yoon, Jin Tae Hong
• Journal: Clinical science (London, England : 1979) (Clin Sci (Lond)) Vol. 128 Issue 10 Pg. 695-706 (May 01 2015) ISSN: 1470-8736 [Electronic] England
• PMID: 25583360 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytochrome P-450 CYP2E1 Inhibitors
• Interleukin-6
• Interleukins
• NF-kappa B
• interleukin-32, mouse
• Ethanol
• Hydrogen Peroxide
• Ptgs2 protein, mouse
• Cyclooxygenase 2
• Aspartate Aminotransferases
• Alanine Transaminase

Topics

• Alanine Transaminase (blood)
• Animals
• Aspartate Aminotransferases (blood)
• Blotting, Western
• Cyclooxygenase 2 (metabolism)
• Cytochrome P-450 CYP2E1 Inhibitors (pharmacology, therapeutic use)
• Electrophoretic Mobility Shift Assay
• Ethanol (administration & dosage, adverse effects)
• Gene Expression Regulation, Enzymologic (drug effects)
• Hepatocytes (metabolism)
• Histological Techniques
• Humans
• Hydrogen Peroxide (metabolism)
• Immunohistochemistry
• Inflammation (drug therapy)
• Interleukin-6 (metabolism)
• Interleukins (genetics, pharmacology, therapeutic use)
• Liver (metabolism)
• Liver Diseases, Alcoholic (drug therapy)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• NF-kappa B (metabolism)
• Real-Time Polymerase Chain Reaction