II. Alcoholic liver injury involves activation of Kupffer cells by endotoxin.

@article{Thurman1998IIAL,
  title={II. Alcoholic liver injury involves activation of Kupffer cells by endotoxin.},
  author={Ronald G. Thurman},
  journal={The American journal of physiology},
  year={1998},
  volume={275 4},
  pages={
          G605-11
        }
}
  • R. Thurman
  • Published 1998
  • Medicine
  • The American journal of physiology
It is well known that females show a greater susceptibility to alcohol-induced liver injury than males. Additionally, females who consume alcohol regularly and have been obese for 10 years or more are at greater risk for both hepatitis and cirrhosis. Female rats on an enteral alcohol protocol exhibit injury more quickly than males, with widespread fatty changes over a larger portion of the liver lobule. Levels of plasma endotoxin, intercellular adhesion molecule-1, free radical adducts… 
Pathogenesis of alcoholic liver disease: newer mechanisms of injury.
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  • Biology, Medicine
    The Keio journal of medicine
  • 1999
TLDR
Advances suggest a number of new approaches as therapy for alcoholic liver injury, including stimulation of Kupffer cells by portal vein endotoxin as a cause of release of cytokines and chemokines, hepatocyte hyper-metabolism, and activation of HSC.
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TLDR
The isolation and culture of Kupffer cells is an important technique with which one can elucidate the mechanisms that contribute to alcoholic liver injury.
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TLDR
Alcohol abuse accounts for more than half of the prev-alence of liver fibrosis and cirrhosis in the western world and features several special characteristics, including elevated gut-derived endotoxinplasma levels.
Lipopolysaccharide-mediated signal transduction: Stabilization of TNF-alpha mRNA contributes to increased lipopolysaccharide-stimulated TNF-alpha production by Kupffer cells after chronic ethanol feeding
TLDR
This model proposes that increased exposure of Kupffer cells to LPS during chronic ethanol consumption results in increased production of inflammatory mediators, in particular TNF-alpha and reactive oxygen species, leading to the progression of fatty liver, inflammation and fibrosis, characteristic of ALD.
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TLDR
The role of innate immune system and oxidative stress caused by gut-derived endotoxin is described and shown that Kupffer cells activation by endotoxin via Toll-like receptor (TLR-4) is involved in alcohol-induced liver injury and that ethanol-induced oxidative stress is important in the regulation of transcription factor NF-kappaB activation.
Role of Lipopolysaccharide-Binding Protein in Early Alcohol-Induced Liver Injury in Mice1
TLDR
Data from a long-term intragastric ethanol feeding model are consistent with the hypothesis that LBP plays an important role in early alcohol-induced liver injury by enhancing LPS-induced signal transduction, most likely in Kupffer cells.
Molecular Mechanisms of Alcohol-Induced Hepatic Fibrosis
TLDR
Sophisticated molecular approaches are underway, aiming to specifically blunt profibrogenic signaling pathways in liver cells or specifically induce cell death in activated hepatic stellate cells to decrease the scarring of the liver.
NADPH oxidase-derived free radicals are key oxidants in alcohol-induced liver disease.
TLDR
The hypothesis that free radicals from NADPH oxidase in hepatic Kupffer cells play a predominant role in the pathogenesis of early alcohol-induced hepatitis by activating NF-kappaB, which activates production of cytotoxic TNF-alpha is strongly supported.
Critical Roles of Kupffer Cells in the Pathogenesis of Alcoholic Liver Disease: From Basic Science to Clinical Trials
TLDR
The critical roles of KCs and related inflammatory cascade in the pathogenesis of ALD make it a promising target in pharmaceutical drug developments for ALD treatment and the combination of these potentially therapeutic drugs with hepatoprotective agents may bring encouraging results.
Reduced Early Alcohol-Induced Liver Injury in CD14-Deficient Mice1
TLDR
Chronic ethanol feeding caused more severe liver injury in wild-type than CD14 knockouts, supporting the hypothesis that endotoxin acting via CD14 plays a major role in the development of early alcohol-induced liver injury.
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References

SHOWING 1-10 OF 56 REFERENCES
Inactivation of Kupffer cells prevents early alcohol‐induced liver injury
TLDR
It is demonstrated that GdCl3 prevents alcohol‐induced liver injury and suggest strongly that Kupffer cells participate in the early phases of the disease process and might represent a new approach to clinical management of alcohol‐ induced liver injury.
Estrogen increases sensitivity of hepatic Kupffer cells to endotoxin.
TLDR
Estrogen treatment in vivo sensitizes Kupffer cells to LPS, leading to increased toxic mediator production by the liver, and estrogen treatment increased LPS binding protein mRNA dramatically in liver in 6-24 h.
Antibiotics prevent liver injury in rats following long-term exposure to ethanol.
TLDR
Intestinal sterilization prevented alcohol-induced liver injury in the rat, supporting the idea that hypermetabolism and consequent hypoxia caused by activation of Kupffer's cells by endotoxin is involved in the mechanism.
Female rats exhibit greater susceptibility to early alcohol-induced liver injury than males.
TLDR
The purpose of this study was to determine if an enteral alcohol delivery model could be used to study susceptibility of females to alcohol-induced liver injury and to account for increased hepatic injury due to ethanol in the female.
Antibodies to tumor necrosis factor alfa attenuate hepatic necrosis and inflammation caused by chronic exposure to ethanol in the rat
TLDR
The hypothesis that TNF‐ α plays an important role in inflammation and necrosis in alcohol‐induced liver injury and that treatment with anti‐TNF‐α antibody may be therapeutically useful in this disease is supported.
Free radical adducts in the bile of rats treated chronically with intragastric alcohol: inhibition by destruction of Kupffer cells.
TLDR
Free radical formation in ethanol-treated rats has been detected for the first time in a model that exhibits injury characteristic of human alcoholic injury, and signal intensity correlates with hepatotoxicity.
The effects of acute and chronic alcoholism on tumor necrosis factor and the inflammatory response.
Ethanol intoxication has been shown to suppress selected functions of the immune system, thereby compromising host defenses against bacterial infections. Because the macrophage secretory protein,
Alcohol causes both tolerance and sensitization of rat Kupffer cells via mechanisms dependent on endotoxin.
TLDR
Kupffer cells isolated from rats early after ethanol exhibited tolerance to LPS, whereas sensitization was observed later, suggesting that both of these phenomena are caused by gut-derived endotoxin and that sensitization in K upffer cells is caused by increases in CD14.
Ethanol and diet-induced alterations in Kupffer cell function.
TLDR
The results suggest that early in chronic alcohol consumption, the immune system may be stimulated by ethanol, and that during studies of ethanol-induced changes in immune system function, close attention must be given to potentially confounding effects of the diet.
Severity of liver injury in experimental alcoholic liver disease. Correlation with plasma endotoxin, prostaglandin E2, leukotriene B4, and thromboxane B2.
TLDR
The study shows the importance of endotoxin in the pathogenesis of experimental alcoholic liver disease and suggests that endotoxin modulates production of eicosanoids that contribute to the severity of liver injury.
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