Signalling pathways in alcohol-induced liver inflammation

J Hepatol. 2009 Jun;50(6):1258-66. doi: 10.1016/j.jhep.2009.03.007. Epub 2009 Mar 28.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Ethanol / toxicity*
  • Hepatitis, Alcoholic / etiology
  • Hepatitis, Alcoholic / immunology
  • Hepatitis, Alcoholic / metabolism*
  • Humans
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Kupffer Cells / drug effects
  • Kupffer Cells / metabolism
  • Lipopolysaccharides / toxicity
  • MAP Kinase Signaling System / drug effects
  • Models, Biological
  • Reactive Oxygen Species / metabolism
  • Receptors, Cytokine / metabolism
  • Signal Transduction / drug effects*
  • Toll-Like Receptors / metabolism
  • Transcription Factors / metabolism


  • Cytokines
  • Lipopolysaccharides
  • Reactive Oxygen Species
  • Receptors, Cytokine
  • Toll-Like Receptors
  • Transcription Factors
  • Ethanol