title: Suppressive effect of ethanol on the expression of hepatic asialoglycoprotein receptors augmented by interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha.
abstract: Blood levels of inflammatory-related cytokines, including interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha, are elevated in patients with alcoholic liver diseases. We investigated the effects of these cytokines and ethanol on the expression of hepatic asialoglycoprotein receptors (AGPRs) in a human hepatoblastoma cell line, HepG2. An [125I]-asialo-orosomucoid binding assay showed significant increases in surface AGPR numbers in HepG2 cells by treatment with IL-1beta, IL-6, and TNF-alpha, to levels which were approximately 130% of the values in untreated control cells. However, the enhanced AGPR numbers induced by treatment with these cytokines were markedly suppressed, to 70%-80% of the number in the untreated cells, by treatment with ethanol. Immunological detection of AGPR with a specific antibody demonstrated that the modulation of surface AGPR numbers was correlated with the cellular expression levels of AGPR. These results suggest that, although IL-1beta, IL-6, and TNF-alpha stimulate the synthesis of hepatic AGPR, ethanol suppresses the expression of AGPR augmented by these cytokines. This leads to an increase in serum asialo-orosomucoid levels caused by the disordered catabolism mediated by AGPR in patients with alcoholic liver disease.
authors.affiliation: Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Kato
authors.forename: Y
authors.initials: Y
authors.lastname: Mogi
authors.forename: Y
authors.initials: Y
authors.lastname: Kohgo
authors.forename: R
authors.initials: R
authors.lastname: Takimoto
authors.forename: M
authors.initials: M
authors.lastname: Kobune
authors.forename: H
authors.initials: H
authors.lastname: Hisai
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: K
authors.initials: K
authors.lastname: Takada
authors.forename: Y
authors.initials: Y
authors.lastname: Niitsu
mesh_terms: D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins / Q000096:biosynthesis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism* / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism* / Q000494:pharmacology; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000187:drug effects*; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects* / Q000378:metabolism
chemical_list: D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D007375:Interleukin-1; D015850:Interleukin-6; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol