Alcoholic liver disease and the gut-liver axis.
Alcoholic liver disease (ALD) is one of the leading causes of liver diseases and liver-related death worldwide. Of the many factors that contribute to the pathogenesis of ALD, gut-derived lipopolysaccharide (LPS) plays a central role in induction of steatosis, inflammation, and fibrosis in the liver. In this review, we discuss the mechanisms by which alcohol contributes to increased gut permeability, the activation of Kupffer cells, and the inflammatory cascade by LPS. The role of the Toll-like receptor 4 (TLR4) complex in LPS recognition and the importance of the TLR4-induced signaling pathways are evaluated in ALD.
Department of Medicine, University of Massachusetts Medical School, LRB 215, Worcester, MA 01605, USA. gyongyi.szabo@umassmed.edu
Gyongyi
G
Szabo
Shashi
S
Bala
D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D008108:Liver Diseases, Alcoholic / Q000473:pathology / Q000503:physiopathology*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism
D002492:Central Nervous System Depressants; D004731:Endotoxins; D008070:Lipopolysaccharides; D035683:MicroRNAs; D051197:Toll-Like Receptor 4; D000431:Ethanol