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Signalling pathways in alcohol-induced liver inflammation
Pranoti Mandrekar, Gyongyi Szabo Journal of Hepatology Volume 50, Issue 6, Pages (June 2009) DOI: /j.jhep Copyright © 2009 European Association for the Study of the Liver Terms and Conditions
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Fig. 1 Cells involved in alcoholic liver injury. Alcohol-mediated increase in gut-derived endotoxin with oxidative stress mechanisms sensitizes hepatic macrophages to release inflammatory cytokines such as TNFα, IL-1β, IL-1α and IL-6 that affects stellate cells and hepatocyte functions. Endotoxin also affects stellate cell and endothelial cell activation and contributes to liver injury. Journal of Hepatology , DOI: ( /j.jhep ) Copyright © 2009 European Association for the Study of the Liver Terms and Conditions
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Fig. 2 TLR4 mediated signalling in alcohol-exposed macrophages. Alcohol alters functions of Toll-like receptors TLR4 in the liver resulting in regulation of MyD88 dependent activation of downstream signalling molecules such as IRAK kinase, IKK and NFκB. MyD88-independent, TRIF-dependent activation of IRF3 is also regulated alcohol exposure. Alcohol also induces NADPH oxidase via reactive oxygen species leading to inflammation. Journal of Hepatology , DOI: ( /j.jhep ) Copyright © 2009 European Association for the Study of the Liver Terms and Conditions
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Fig. 3 TLR4 mediated alcohol-exposed macrophages signalling in alcohol-exposed macrophages. Alcohol alters functions of Toll-like receptors TLR4 in the liver resulting in activation of MAP kinases culminating in alteration of binding to transcription factors such as Egr-1, AP-1 and STAT1. Alcohol also affects cytokine mRNA stability via modulation of MAP kinase activity. Journal of Hepatology , DOI: ( /j.jhep ) Copyright © 2009 European Association for the Study of the Liver Terms and Conditions
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