Z Gastroenterol 2007; 45 - A1_09
DOI: 10.1055/s-2007-967763

Potentiation of inflammatory genes expression by triglycerides in rat Kupffer cells

N Budick 1, J Dudas 2, Z Madar 1, G Ramadori 2, O Tirosh 1
  • 1Institute of Biochenistry, Food Science and Nutrition, Faculty of Agricultural, Food and Enviromental Quality Sciences, The Hebrew University of Jerusalem, Rehovot 76100 Israel, Rehovot
  • 2Abteilung Gastroenterologie und Endokrinologie, Georg-August-Universität, Göttingen

Aims: Accumulation of fat in the liver may lead to inflammation and progressive fibrosis. Kupffer cells are important for the clearance of intestinal bacterial products. These cells also participate in inflammatory reactions in the liver. The inflammatory response following exposure of isolated rat Kupffer cells to lipids and to endotoxin was investigated in this study.

Methods: Kupffer cells were treated with lipopolysaccharide (LPS) and triglycerides (TGs) alone or in combination. Gene expression of tumor-necrosis-factor-alpha (TNF alpha), interleukin–1-beta (IL1-beta), interleukin–6 (IL–6), inducible nitric oxide synthetase (iNOS), granulocyte-monocyte colony stimulatory factor (GM-CSF) and granulocyte colony stimulatory factor (GCSF) was measured using real time RT-PCR, the protein expression of iNOS was analysed by western blot. The mechanism for inflammatory gene expression and activity in the presence or absence of lipids was studied by electrophoretic mobility shift assay, reporter gene analysis and treatment with specific inhibitors.

Results: Lipopolysaccharide exposure increased the mRNA expression level of the studied genes. Triglyceride exposure alone showed no significant effects, whereas, in_combination with LPS induction of all these genes was potentiated up to 3.2, 1.4, 2.8, 2,25, 1.7 and 3-fold (TNF-alpha, IL1-beta, IL–6, iNOS, GMCSF, GCSF, respectively) compared with LPS alone. Increased DNA binding of NFkB-alpha transcription factor was found after simultaneous exposure of Kupffer cells to LPS and TGs. TGs alone were found to be able to activate the cyclic AMP response element binding protein (CREB).

Conclusions: For the first time we demonstrate a direct contribution of triglycerides to inflammatory conditions in the liver by increasing the activation of Kupffer cells. This synergistic effect might be mediated by the modification of the NFkB- alpha signalling pathway and by the involvement of CREB activation.