Interleukin-32{gamma} attenuates ethanol-induced liver injury by the inhibition of Cytochrome P450 2E1 expression and inflammatory responses

Alcohol abuse and alcoholism lead to alcoholic liver disease, 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. Here, 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 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 cyclooxyganase-2 and interleukin-6 were reduced in the livers of IL-32γ mice. Because nuclear transcription factor kappa B (NF-κB) is a key redox transcription factor of inflammatory response, we examined NF-κB activity. Ethanol-induced NF-κB activities were significantly lower in the livers of IL-32γ mice than in wild-type mice. Furthermore, reduced infiltra...

Source: Clinical Science - January 13, 2015 Category: Biomedical Science Authors: D Lee, D Kim, C Hwang, S Song, S Han, Y Soo Kim, H Yoo, Y Jung, S Kim, D Yoon, J Tae Hong Source Type: research