title: 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.affiliation: *College of Pharmacy, Chungbuk National University, 48, Gaeshin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Dong Hun
authors.initials: DH
authors.lastname: Lee
authors.affiliation: *College of Pharmacy, Chungbuk National University, 48, Gaeshin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Dae Hwan
authors.initials: DH
authors.lastname: Kim
authors.affiliation: *College of Pharmacy, Chungbuk National University, 48, Gaeshin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Chul Ju
authors.initials: CJ
authors.lastname: Hwang
authors.affiliation: *College of Pharmacy, Chungbuk National University, 48, Gaeshin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Sukgil
authors.initials: S
authors.lastname: Song
authors.affiliation: *College of Pharmacy, Chungbuk National University, 48, Gaeshin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Sang Bae
authors.initials: SB
authors.lastname: Han
authors.affiliation: *College of Pharmacy, Chungbuk National University, 48, Gaeshin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
authors.affiliation: *College of Pharmacy, Chungbuk National University, 48, Gaeshin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Hwan Soo
authors.initials: HS
authors.lastname: Yoo
authors.affiliation: †College of Pharmacy, Pusan National University, 2, Busandaehak-ro 63beon-gil, Geumjeong-gu, Busan 609-735, Republic of Korea.
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Jung
authors.affiliation: ‡Department of Biomedical science and Technology, Bio/Molecular Informatics Center, Konkuk University, 1, Hwayang-dong, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: §Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, 1, Hwayang-dong, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Do Young
authors.initials: DY
authors.lastname: Yoon
authors.affiliation: *College of Pharmacy, Chungbuk National University, 48, Gaeshin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015153:Blotting, Western; D051546:Cyclooxygenase 2 / Q000378:metabolism; D065691:Cytochrome P-450 CYP2E1 Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D024202:Electrophoretic Mobility Shift Assay; D000431:Ethanol / Q000008:administration & dosage / Q000009:adverse effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D022781:Hepatocytes / Q000378:metabolism; D006652:Histological Techniques; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007150:Immunohistochemistry; D007249:Inflammation / Q000188:drug therapy*; D015850:Interleukin-6 / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000494:pharmacology* / Q000627:therapeutic use; D008099:Liver / Q000378:metabolism; D008108:Liver Diseases, Alcoholic / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D065691:Cytochrome P-450 CYP2E1 Inhibitors; D015850:Interleukin-6; D007378:Interleukins; D016328:NF-kappa B; C569037:interleukin-32, mouse; D000431:Ethanol; D006861:Hydrogen Peroxide; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase