Alcoholic Liver Disease: Role of Cytokines.
The present review spans a broad spectrum of topics dealing with alcoholic liver disease (ALD), including clinical and translational research. It focuses on the role of the immune system and the signaling pathways of cytokines in the pathogenesis of ALD. An additional factor that contributes to the pathogenesis of ALD is lipopolysaccharide (LPS), which plays a central role in the induction of steatosis, inflammation, and fibrosis in the liver. LPS derived from the intestinal microbiota enters the portal circulation, and is recognized by macrophages (Kupffer cells) and hepatocytes. In individuals with ALD, excessive levels of LPS in the liver affect immune, parenchymal, and non-immune cells, which in turn release various inflammatory cytokines and recruit neutrophils and other inflammatory cells. In this review, we elucidate the mechanisms by which alcohol contributes to the activation of Kupffer cells and the inflammatory cascade. The role of the stellate cells in fibrogenesis is also discussed.
In Vitro Drug Safety and Biotechnology, University of Toronto, Toronto, ON M5G 0A3, Canada. manuela.neuman@utoronto.ca.|Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, ON M5G 0A3, Canada. manuela.neuman@utoronto.ca.
Manuela G
MG
Neuman
Division of Gastroenterology, Kaplan Health Sciences Centre, Department of Medicine, Faculty of Medicine, Hebrew University, Rehovot 76100, Israel. halishy@netvision.net.il.
Yaakov
Y
Maor
In Vitro Drug Safety and Biotechnology, University of Toronto, Toronto, ON M5G 0A3, Canada. radu.nanau@utoronto.ca.
Radu M
RM
Nanau
Division of Gastroenterology, Kaplan Health Sciences Centre, Department of Medicine, Faculty of Medicine, Hebrew University, Rehovot 76100, Israel. ehudm@clalit.org.il.
Ehud
E
Melzer
Israel Anti-Drug Authority, Jerusalem 91039, Israel. haimm@antidrugs.gov.il.
Haim
H
Mell
In Vitro Drug Safety and Biotechnology, University of Toronto, Toronto, ON M5G 0A3, Canada. M_neuman@rogers.com.|Casa de Ajutor Reciproc, Bucharest 031621, Romania. M_neuman@rogers.com.
Mihai
M
Opris
Sunnybrook Health Sciences Centre and Department of Internal Medicine, University of Toronto, Toronto, ON M5G 0A3, Canada. lawrence.cohen@sunnybrook.ca.
Lawrence
L
Cohen
Division of Gastroenterology, Kaplan Health Sciences Centre, Department of Medicine, Faculty of Medicine, Hebrew University, Rehovot 76100, Israel. stephen@malnick.net.
Stephen
S
Malnick
D000437:Alcoholism / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism; D008108:Liver Diseases, Alcoholic / Q000378:metabolism*
D016207:Cytokines; D008070:Lipopolysaccharides
Toll-like receptor; alcoholic liver disease; hepatocellular carcinoma; lipopolysaccharide; transforming growth factor; tumor necrosis factor