Signalling pathways in alcohol-induced liver inflammation
Department of Medicine, Division of Gastroenterology; Department of Medicine, Rheumatology Division
Medical Subject Headings
Animals; Cytokines; Ethanol; Hepatitis, Alcoholic; Humans; Killer Cells, Natural; Kupffer Cells; Lipopolysaccharides; MAP Kinase Signaling System; Models, Biological; Reactive Oxygen Species; Receptors, Cytokine; Signal Transduction; Toll-Like Receptors; Transcription Factors
Gastroenterology | Hepatology | Immunology and Infectious Disease
The pathogenesis of alcoholic liver injury involves interactions of several intracellular signalling pathways in different cell types of the liver. Alcohol-induced sensitization of liver macrophages to portal endotoxin/lipopolysaccharide (LPS) is considered a hallmark of alcoholic liver disease (ALD). Intracellular mechanisms associated with LPS-induced signalling play a crucial role in the initiation and progression of alcoholic liver injury, and are being extensively explored. LPS recognition by Toll-like receptor 4 (TLR4) on macrophages and other cell types in the liver, activation of downstream signalling pathways culminating in activation of transcription factors such as NFkappaB, AP-1 leads to increased inflammatory cytokine production in ALD. In addition, LPS-induced MAPK such as ERK and p38 also contribute to liver injury. The importance of alcohol-induced reactive oxygen species and interactions with TLR pathways in macrophages leading to inflammation is becoming increasingly evident. Collectively, these signalling pathways induce pro- and anti-inflammatory cytokines that play an important role in ALD. In this review we describe the key signalling intermediates leading to alcohol-induced inflammation in alcoholic liver disease.
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Citation: J Hepatol. 2009 Jun;50(6):1258-66. Epub 2009 Mar 28. Link to article on publisher's site
Mandrekar, Pranoti and Szabo, Gyongyi, "Signalling pathways in alcohol-induced liver inflammation" (2009). Gastroenterology Publications and Presentations. 78.