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Kupffer Cell Sensitization By Alcohol Involves Increased Permeability To Gut-derived Endotoxin.

Nobuyuki Enomoto, Kenichi Ikejima, Shunhei Yamashina, Miyoko Hirose, Hiroko Shimizu, Tsuneo Kitamura, Yoshifumi Takei, N Sato And, Ronald G. Thurman
Published 2001 · Psychology, Medicine
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BACKGROUND Studies with gut sterilization and Kupffer cell inactivation support the hypothesis that endotoxin and Kupffer cells are involved in mechanisms of alcohol-induced liver injury. Recently, we found that Kupffer cells isolated from rats treated only once with ethanol were sensitized to endotoxin 24 hr later. Moreover, we established a new, simple animal model of ethanol hepatotoxicity based on Kupffer cell sensitization. The purpose of this study was to determine the mechanisms by which alcohol sensitizes Kupffer cells to lipopolysaccharide (LPS). METHODS Female Wistar rats were given ethanol (5 g/kg body weight) once every 24 hr intragastrically, and ethanol concentration, ethanol elimination, and portal vein endotoxin were measured. Gut permeability was measured in isolated segments of ileum by translocation of horseradish peroxidase. Kupffer cells were isolated 24 hr after ethanol administration in vivo and were cultured in RPMI 1640 with 10% fetal bovine serum. After the addition of LPS, intracellular Ca2+ was measured by using a microspectrofluorometer with the fluorescent indicator fura-2, and tumor necrosis factor (TNF)-alpha was measured by enzyme-linked immunosorbent assay. CD14 was evaluated by Western analysis. RESULTS Ethanol levels exhibited a cyclic pattern in ethanol-treated rats. Similar results were obtained in groups given ethanol and antibiotics for 4 weeks. Rates of alcohol elimination were around 3.5 mmol/kg/hr in control rats. After 4 weeks of ethanol treatment with or without antibiotics, elimination rates were not changed. Translocation of horseradish peroxidase was increased about 3-fold in gut segments by treatment with ethanol. This increase was not altered by treatment with antibiotics. Moreover, portal vein endotoxin levels were increased from nearly undetectable levels to 80 pg/ml in plasma of rats treated with ethanol. As expected, this increase was prevented (<20 pg/ml) by antibiotics. In isolated Kupffer cells from rats treated with ethanol for 4 weeks, CD14, LPS-induced intracellular Ca2+, and TNF-alpha all were increased. These phenomena were blocked by antibiotics. CONCLUSIONS Kupffer cells isolated from rats treated with ethanol for 4 weeks exhibit sensitization to LPS. It is likely that increased permeability of the gut is a prominent event that leads to alcoholic liver injury.

This paper is referenced by
Rôle des cellules de Kupffer et du microbiote intestinal dans les hépatopathies métaboliques
Gladys Ferrere (2015)
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Damien Naslain (2009)
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B. Ametaj (2010)
Lipopolysaccharide-induced liver injury in rats treated with the CYP2E1 inducer pyrazole.
Yongke Lu (2005)
Contribution of Gut Bacteria to Liver Pathobiology
Gakuhei Son (2010)
Lipopolysaccharides in liver injury: molecular mechanisms of Kupffer cell activation.
Grace L. Su (2002)
Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability
Patrice D Cani (2009)
Amanda M. McLean (2019)
Protective effects of hypothalamic beta-endorphin neurons against alcohol-induced liver injuries and liver cancers in rat animal models.
Sengottuvelan Murugan (2014)
Metagenomics of the human body
Karen E. Nelson (2011)
Interplay between rumen digestive disorders and diet-induced inflammation in dairy cattle.
Qendrim Zebeli (2012)
Microbial Ecology in Health and Disease
Stephen M. Riordan (2008)
Rodent Models and Imaging Techniques to Study Liver Regeneration
Weiwei Wei (2014)
The anti-inflammatory, anti-oxidant and protective effects of probiotic mixture on organ toxicity in a rat model.
M. Karamese (2020)
Manipulation of nitric oxide in an animal model of acute liver injury. The impact on liver and intestinal function
Diya Adawi (2007)
Animal Models of Alcoholic Liver Disease—Focus on the Intragastric Feeding Model
Amin A. Nanji (2003)
Involvement of Toll-like receptor 4 in acetaminophen hepatotoxicity.
Herbert C. Yohe (2006)
Signaling Pathways in Liver Diseases Kupffer Cells
Christian J. Steib (2010)
Nonalcoholic steatosis and steatohepatitis IV. Nonalcoholic fatty liver disease abnormalities in macrophage function and cytokines.
Anna Mae Diehl (2002)
Review: Enhancing gastrointestinal health in dairy cows.
J. C. Plaizier (2018)
Macrophage Phenotype and Function in Liver Disorder
Lang Dou (2019)
Microbiome and Diseases: Hepatic Disorders
Ina Bergheim (2018)
Chinese medicinal formula, Qinggan Huoxue Recipe protects rats from alcoholic liver disease via the lipopolysaccharide-Kupffer cell signal conduction pathway
Tao Wu (2014)
TLR4 signaling and the inhibition of liver hepcidin expression by alcohol.
Emily M Zmijewski (2014)
Direct Hepatotoxic Effect of KC Chemokine in the Liver Without Infiltration of Neutrophils
Lela Stefanovic (2005)
Osteopontin binding to lipopolysaccharide lowers tumor necrosis factor-α and prevents early alcohol-induced liver injury in mice.
Xiaodong Ge (2014)
Effect of acute and chronic red wine consumption on lipopolysaccharide concentrations.
Mercedes Clemente-Postigo (2013)
The gut microbiome as therapeutic target.
Patrice D Cani (2011)
Alcoholic liver disease
H. Seitz (2018)
Graptopetalum Paraguayense Ameliorates Chemical-Induced Rat Hepatic Fibrosis In Vivo and Inactivates Stellate Cells and Kupffer Cells In Vitro
Li-Jen Su (2013)
Gut microbiome changes in Nonalcoholic fatty liver disease & alcoholic liver disease
Eric K. Kwong (2020)
Changes in Gut Microbiota Control Metabolic Endotoxemia-Induced Inflammation in High-Fat Diet–Induced Obesity and Diabetes in Mice
Patrice D Cani (2008)
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