title: The unfolding web of innate immune dysregulation in alcoholic liver injury.
abstract: Inflammatory cell and cytokine cascade activation is present in humans with alcoholic liver disease as well as in animal models of alcohol-induced liver damage. Gut-derived lipopolysaccharide (LPS), a ligand of the Toll-like receptor 4 (TLR4), plays a central role in triggering and maintaining activation of Kupffer cells in alcoholic hepatitis. In this mini-review, we describe molecular mechanisms that lead to increased inflammatory cell activation by alcohol and LPS and discuss the mechanism for activation in alcohol-exposed macrophages. In alcohol-induced liver disease we discuss the role of MyD88-independent but IRF3-mediated TLR4 signaling in alcohol-related liver inflammation and liver damage.
authors.affiliation: University of Massachusetts Medical School, Worcester, 01605, USA. gyongyi.szabo@umassmed.edu
authors.forename: G
authors.initials: G
authors.lastname: Szabo
authors.forename: P
authors.initials: P
authors.lastname: Mandrekar
authors.forename: J
authors.initials: J
authors.lastname: Petrasek
authors.forename: D
authors.initials: D
authors.lastname: Catalano
mesh_terms: D000437:Alcoholism / Q000276:immunology* / Q000503:physiopathology; D000818:Animals; D041981:Gastrointestinal Tract / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D008099:Liver / Q000276:immunology / Q000378:metabolism; D008108:Liver Diseases, Alcoholic / Q000276:immunology* / Q000503:physiopathology; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000378:metabolism
chemical_list: C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4