Triglycerides potentiate the inflammatory response in rat Kupffer cells.
Accumulation of fat in the liver, also known as steatosis, may lead to inflammation and tissue damage. Kupffer cells (KCs) are the resident macrophages of the liver and have an important role in inflammatory reactions. The inflammatory response of isolated rat KCs to endotoxin in the presence of lipids was investigated in this study. KCs were treated with lipopolysaccharide (LPS) and triglycerides (TGs) alone or in combination. TGs had no effect on the expression of pro-inflammatory mediators, but adding TGs to LPS enhanced the induction of inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and granulocyte colony-stimulating factor (G-CSF), compared with LPS treatment alone. Increased DNA binding of NF-kappaB transcription factor was seen on simultaneous exposure of the cells to TGs and LPS, which was accompanied by decreased intracellular ROS production and increased GSH levels. The inflammation-potentiating effect of TGs on iNOS expression was abolished on NF-kappaB inhibition. This enhanced inflammatory response might indicate a contribution of lipids to the inflammatory conditions in the fatty liver by increased activation of KCs.
Budick-Harmelin
Noga
N
The School of Nutritional Sciences, Institute of Biochemistry, Food Science and Nutrition, Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew University of Jerusalem, Israel.
Dudas
Jozsef
J
Demuth
Julia
J
Madar
Zecharia
Z
Ramadori
Giuliano
G
Tirosh
Oren
O
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004357:Drug Synergism; D015870:Gene Expression / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D007728:Kupffer Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013450:Sulfones / Q000494:pharmacology; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014280:Triglycerides / Q000494:pharmacology*; D015054:Zymosan / Q000494:pharmacology
C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; C507781:Myd88 protein, rat; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D009570:Nitriles; D017382:Reactive Oxygen Species; D013450:Sulfones; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D014280:Triglycerides; D015054:Zymosan; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D005978:Glutathione