Signalling pathways in alcohol-induced liver inflammation

Pranoti Mandrekar, Gyongyi Szabo

Research output: Contribution to journalReview article

271 Citations (Scopus)

Abstract

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 NFκB, 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.

Original languageEnglish
Pages (from-to)1258-1266
Number of pages9
JournalJournal of Hepatology
Volume50
Issue number6
DOIs
Publication statusPublished - Jun 1 2009

Keywords

  • Kupffer cells
  • MAP kinases
  • Macrophages
  • TLRs
  • Transcription factors

ASJC Scopus subject areas

  • Hepatology

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