Signalling pathways in alcohol-induced liver inflammation

Pranoti Mandrekar, G. Szabó

Research output: Contribution to journalReview article

258 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 2009

Fingerprint

Alcoholic Liver Diseases
Alcohols
Inflammation
Lipopolysaccharides
Liver
Macrophages
Wounds and Injuries
Cytokines
Toll-Like Receptor 4
Transcription Factor AP-1
Endotoxins
Reactive Oxygen Species
Anti-Inflammatory Agents
Transcription Factors

Keywords

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

ASJC Scopus subject areas

  • Hepatology

Cite this

Signalling pathways in alcohol-induced liver inflammation. / Mandrekar, Pranoti; Szabó, G.

In: Journal of Hepatology, Vol. 50, No. 6, 06.2009, p. 1258-1266.

Research output: Contribution to journalReview article

Mandrekar, Pranoti ; Szabó, G. / Signalling pathways in alcohol-induced liver inflammation. In: Journal of Hepatology. 2009 ; Vol. 50, No. 6. pp. 1258-1266.
@article{8bdb2083a9f24cd9b413467d194ed4a7,
title = "Signalling pathways in alcohol-induced liver inflammation",
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.",
keywords = "Kupffer cells, Macrophages, MAP kinases, TLRs, Transcription factors",
author = "Pranoti Mandrekar and G. Szab{\'o}",
year = "2009",
month = "6",
doi = "10.1016/j.jhep.2009.03.007",
language = "English",
volume = "50",
pages = "1258--1266",
journal = "Journal of Hepatology",
issn = "0168-8278",
publisher = "Elsevier",
number = "6",

}

TY - JOUR

T1 - Signalling pathways in alcohol-induced liver inflammation

AU - Mandrekar, Pranoti

AU - Szabó, G.

PY - 2009/6

Y1 - 2009/6

N2 - 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.

AB - 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.

KW - Kupffer cells

KW - Macrophages

KW - MAP kinases

KW - TLRs

KW - Transcription factors

UR - http://www.scopus.com/inward/record.url?scp=67349255858&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67349255858&partnerID=8YFLogxK

U2 - 10.1016/j.jhep.2009.03.007

DO - 10.1016/j.jhep.2009.03.007

M3 - Review article

C2 - 19398236

AN - SCOPUS:67349255858

VL - 50

SP - 1258

EP - 1266

JO - Journal of Hepatology

JF - Journal of Hepatology

SN - 0168-8278

IS - 6

ER -