Fat diet and alcohol-induced steatohepatitis after LPS challenge in mice: role of bioactive TNF and Th1 type cytokines

Autor: Laurent Spahr, Antoine Hadengue, Dominique Vesin, Irene Garcia, Maria Luisa Galve Martin, Marie-Laure Santiago-Raber, Agathe L. Fotio, Maria L. Olleros, Laura Rubbia-Brandt
Jazyk: angličtina
Rok vydání: 2008
Předmět:
Lipopolysaccharides
Liver cytology
RNA
Messenger/metabolism
Nitric Oxide Synthase Type II
ddc:616.07
Interleukin-6/physiology
Biochemistry
Interferon-gamma/physiology
Mice
Immunology and Allergy
Fatty Liver
Alcoholic/pathology/physiopathology
Liver injury
Interleukin-12 Subunit p40
Fatty liver
Hematology
Liver
Neutrophil Infiltration
Cytokines
Ethanol/adverse effects
Tumor necrosis factor alpha
Female
Cytokines/physiology
Nitric Oxide Synthase Type II/metabolism
Fatty Liver
Alcoholic
medicine.medical_specialty
Immunology
Interleukin-12 Subunit p40/physiology
Liver/cytology
Fatty Liver/etiology/pathology
Interferon-gamma
Enzyme activator
Insulin resistance
Tumor Necrosis Factor-alpha/physiology
Internal medicine
medicine
Animals
Th1 Cells/immunology
RNA
Messenger
Molecular Biology
Peroxidase
Ethanol
Interleukin-6
Tumor Necrosis Factor-alpha
business.industry
Th1 Cells
medicine.disease
Dietary Fats
Obesity
Fatty Liver
Enzyme Activation
Mice
Inbred C57BL
Disease Models
Animal
Endocrinology
Dietary Fats/pharmacology
Steatohepatitis
business
Peroxidase/metabolism
Zdroj: Cytokine, Vol. 44, No 1 (2008) pp. 118-25
ISSN: 1096-0023
Popis: Obesity with insulin resistance and alcohol are the most frequent causes of steatohepatitis. This work investigates the contribution of bioactive TNF and Th1 type cytokines in a mouse model of steatohepatitis induced by FAT alone or FAT+EtOH and endotoxin. The extent of liver injury and cytokine activation induced by endotoxin in chronic FAT-fed mice, FAT+EtOH-fed mice, or mice fed standard chow were analyzed. Endotoxin administration to either FAT-fed or FAT+EtOH-fed mice increased serum ALT and AST compared to standard chow mice. Immunoreactive TNF was strongly activated by LPS in FAT-fed and FAT+EtOH-fed mice which presented the highest levels, but low levels were found in standard chow mice. In contrast, bioactive TNF was only present in serum of FAT-fed and in particular the highest levels were found in FAT+EtOH-fed mice. Moreover, soluble TNFR2 but not TNFR1 was found in lower amounts in serum of FAT+EtOH-fed mice compared to FAT-fed mice. Steatohepatitis was associated with increased IL-6, IFN-gamma, and iNOS mRNA and proteins. Data show that a moderately FAT diet and low-dose EtOH concur to generate steatohepatitis and TNF liver expression after LPS. In this model, changes in the regulation of TNF are associated with increased expression of IL-6, IFN-gamma, and iNOS.
Databáze: OpenAIRE
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