Financial support: This work was supported in part by National Institutes of Health grant RO1AA011975, RO1 AA16399 and P20AA17069 to LEN and F31AA016434 to JIC.
Pathogenesis of alcoholic liver disease: interactions between parenchymal and non-parenchymal cells
Version of Record online: 30 JAN 2011
© 2011 The Authors. Journal of Digestive Diseases © 2011 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.
Journal of Digestive Diseases
Volume 12, Issue 1, pages 3–9, February 2011
How to Cite
COHEN, J. I. and NAGY, L. E. (2011), Pathogenesis of alcoholic liver disease: interactions between parenchymal and non-parenchymal cells. Journal of Digestive Diseases, 12: 3–9. doi: 10.1111/j.1751-2980.2010.00468.x
- Issue online: 30 JAN 2011
- Version of Record online: 30 JAN 2011
- Accepted manuscript online: 17 NOV 2010 11:15PM EST
- innate immunity;
- Kupffer cells
The development of alcoholic liver disease (ALD) is a complex process involving both the parenchymal and non-parenchymal cells in the liver. The impact of ethanol on hepatocytes can be characterized as a condition of organelle stress with multifactorial changes in hepatocellular function accumulating during ethanol exposure. These changes include oxidative stress, mitochondrial dysfunction, decreased methylation capacity, endoplasmic reticulum stress, impaired vesicular trafficking and altered proteasome function. Injury to hepatocytes is attributed, in part, to ethanol metabolism by the hepatocytes. Changes in the structural integrity of hepatic sinusoidal endothelial cells, as well as enhanced inflammation in the liver during ethanol exposure are also important contributors to injury. Activation of hepatic stellate cells initiates the deposition of extracellular matrix proteins characteristic of fibrosis. Kupffer cells, the resident macrophages in the liver, are particularly critical to the onset of ethanol-induced liver injury. Chronic ethanol exposure sensitizes Kupffer cells to activation by lipopolysaccharides via toll-like receptor 4. This sensitization enhances the production of inflammatory mediators, such as tumor necrosis factor-α and reactive oxygen species that contribute to hepatocyte dysfunction, necrosis and apoptosis of hepatocytes and the generation of extracellular matrix proteins leading to fibrosis. In this review we provide an overview of the complex interactions between parenchymal and non-parenchymal cells in the liver during the progression of ethanol-induced liver injury.