title: Role of Kupffer cells and gut-derived endotoxins in alcoholic liver injury.
abstract: The hepatotoxic effects of alcohol have been described in detail, but factors responsible for its hepatotoxicity have only partially been characterized. For example, it is known that chronic ethanol ingestion increases hepatotoxicity and produces fatty liver, hepatitis and cirrhosis. However, acute ethanol consumption reduces endotoxin hepatotoxicity. It now appears that Kupffer cells participate in several aspects of these phenomena. Previously, most studies on the effects of alcohol on liver function have focused chiefly on the hepatocyte. Recently, attention has been directed towards the effect of ethanol ingestion on Kupffer cell function, which is stimulated by gut-derived endotoxins (lipopolysaccharides) via mechanisms dependent on increased gut permeability and the possible relationship between Kupffer cells and alcohol-induced liver injury. Here we will review new evidence for the proposal that Kupffer cells and endotoxins play a pivotal role in hepatotoxicity following alcohol exposure, based on studies using the continuous intragastric enteral feeding model developed by Tsukamoto and French and an acute model developed by us.
authors.affiliation: Department of Pharmacology, University of North Carolina at Chapel Hill, USA.
authors.forename: N
authors.initials: N
authors.lastname: Enomoto
authors.forename: K
authors.initials: K
authors.lastname: Ikejima
authors.forename: B U
authors.initials: BU
authors.lastname: Bradford
authors.forename: C A
authors.initials: CA
authors.lastname: Rivera
authors.forename: H
authors.initials: H
authors.lastname: Kono
authors.forename: M
authors.initials: M
authors.lastname: Goto
authors.forename: S
authors.initials: S
authors.lastname: Yamashina
authors.forename: P
authors.initials: P
authors.lastname: Schemmer
authors.forename: T
authors.initials: T
authors.lastname: Kitamura
authors.forename: H
authors.initials: H
authors.lastname: Oide
authors.forename: Y
authors.initials: Y
authors.lastname: Takei
authors.forename: M
authors.initials: M
authors.lastname: Hirose
authors.forename: H
authors.initials: H
authors.lastname: Shimizu
authors.forename: A
authors.initials: A
authors.lastname: Miyazaki
authors.forename: D A
authors.initials: DA
authors.lastname: Brenner
authors.forename: N
authors.initials: N
authors.lastname: Sato
authors.forename: R G
authors.initials: RG
authors.lastname: Thurman
mesh_terms: D000431:Ethanol / Q000494:pharmacology; D005260:Female; D006801:Humans; D007728:Kupffer Cells / Q000502:physiology*; D008070:Lipopolysaccharides / Q000378:metabolism*; D008108:Liver Diseases, Alcoholic / Q000209:etiology*; D008297:Male; D012737:Sex Factors
chemical_list: D008070:Lipopolysaccharides; D000431:Ethanol