title: The role of Kupffer cell oxidant production in early ethanol-induced liver disease.
abstract: Considerable evidence for a role of Kupffer cells in alcoholic liver disease has accumulated and they have recently been shown to be a predominant source of free radicals. Several approaches including pharmacological agents, knockout mice, and viral gene transfer have been used to fill critical gaps in understanding key mechanisms by which Kupffer cell activation, oxidant formation, and cytokine production lead to liver damage and subsequent pathogenesis. This review highlights new data in support of the hypothesis that Kupffer cells play a pivotal role in hepatotoxicity due to ethanol by producing oxidants via NADPH oxidase.
authors.affiliation: Laboratory of Hepatobiology and Toxicology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7365, USA. wheelmi@med.unc.edu
authors.forename: M D
authors.initials: MD
authors.lastname: Wheeler
authors.forename: H
authors.initials: H
authors.lastname: Kono
authors.forename: M
authors.initials: M
authors.lastname: Yin
authors.forename: M
authors.initials: M
authors.lastname: Nakagami
authors.forename: T
authors.initials: T
authors.lastname: Uesugi
authors.forename: G E
authors.initials: GE
authors.lastname: Arteel
authors.forename: E
authors.initials: E
authors.lastname: Gäbele
authors.forename: I
authors.initials: I
authors.lastname: Rusyn
authors.forename: S
authors.initials: S
authors.lastname: Yamashina
authors.forename: M
authors.initials: M
authors.lastname: Froh
authors.forename: Y
authors.initials: Y
authors.lastname: Adachi
authors.forename: Y
authors.initials: Y
authors.lastname: Iimuro
authors.forename: B U
authors.initials: BU
authors.lastname: Bradford
authors.forename: O M
authors.initials: OM
authors.lastname: Smutney
authors.forename: H D
authors.initials: HD
authors.lastname: Connor
authors.forename: R P
authors.initials: RP
authors.lastname: Mason
authors.forename: S M
authors.initials: SM
authors.lastname: Goyert
authors.forename: J M
authors.initials: JM
authors.lastname: Peters
authors.forename: F J
authors.initials: FJ
authors.lastname: Gonzalez
authors.forename: R J
authors.initials: RJ
authors.lastname: Samulski
authors.forename: R G
authors.initials: RG
authors.lastname: Thurman
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D000975:Antioxidants / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity*; D016166:Free Radical Scavengers / Q000627:therapeutic use; D006801:Humans; D007728:Kupffer Cells / Q000378:metabolism* / Q000502:physiology; D008108:Liver Diseases, Alcoholic / Q000188:drug therapy / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D016877:Oxidants / Q000096:biosynthesis*; D018124:Receptors, Tumor Necrosis Factor / Q000172:deficiency / Q000235:genetics; D047888:Receptors, Tumor Necrosis Factor, Type I; D019076:Transgenes / Q000502:physiology
chemical_list: D015703:Antigens, CD; D000975:Antioxidants; D016166:Free Radical Scavengers; D016877:Oxidants; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D000431:Ethanol