The role of Kupffer cell oxidant production in early ethanol-induced liver disease.
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.
Wheeler
M D
MD
Laboratory of Hepatobiology and Toxicology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7365, USA. wheelmi@med.unc.edu
Kono
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Yin
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Nakagami
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Uesugi
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Arteel
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Gäbele
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Rusyn
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Yamashina
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Froh
M
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Adachi
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Y
Iimuro
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Bradford
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Smutney
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Connor
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Mason
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Goyert
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Peters
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Gonzalez
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Samulski
R J
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Thurman
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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
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