title: Anti-inflammatory strategies in alcoholic steatohepatitis.
abstract: The hepatotoxic effects of alcohol have been described in detail, but mechanisms underlying the hepatotoxicity have been only partially characterized. Recently, increasing lines of evidence indicate that Kupffer cells play multiple roles in initiation and progression of alcoholic steatohepatitis. After ethanol exposure, Kupffer cells are activated via a mechanism dependent on gut-derived endotoxin, and release active mediators such as proinflammatory cytokines and eicosanoids. These mediators are responsible for the pathophysiology of alcoholic steatohepatitis. This review discusses the current concept of Kupffer cell-mediated steatohepatitis and how it relates to the hypothesis on the mechanism by which alcoholic steatohepetitis is caused, as well as several key issues that have to be addressed in this field: (i) How do Kupffer cells undergo priming and activation during alcoholic steatohepatitis?; (ii) What kind of mediators are involved?; and (iii) How does the concept translate into a strategy for therapeutics of alcoholic steatohepatitis?
authors.affiliation: Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Enomoto
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Takei
authors.forename: Shunhei
authors.initials: S
authors.lastname: Yamashina
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ikejima
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Kitamura
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Sato
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D000431:Ethanol / Q000633:toxicity*; D005234:Fatty Liver / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007728:Kupffer Cells / Q000187:drug effects / Q000473:pathology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008108:Liver Diseases, Alcoholic / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol