Einfluss von freien Fettsäuren und Triglyceriden auf die Expression von proinflammatorischen Mediatoren und Adhäsionsmolekülen in Hepatozyten und Kupffer-Zellen (der Ratte)

Abstract

The Non-alcoholic fatty liver diseases is one of the most common liver disease worldwide. Previously published datas from clinical and animal studies imply that the early forms of this disease, steatosis and steatohepatitis, are due to excessive exposure to free fatty acids and inflammatory cytokines. The exact pathogenic mechanism, which describes the progression of NAFLD to the severe manifestation of NASH, is not yet understood enough. One assumes, however, that different cell populations are involved in different ways in this disease process. In this study should clarify the extent to which fat exposure plays a role in a possible induction or maintenance of an inflammatory response. This was specifically investigated the changes in gene expression of proinflammatory mediators in hepatocytes and Kupffer cell populations under the administration of triglycerides and free fatty acids. Data of this thesis have shown that the sole application of triglycerides causes no change in gene expression of proinflammatory mediators, both in hepatocytes and in Kupffer cells of the rat. On the other hand, the acquired data could indicate that the exposure of fat also may have a liver cell protective effect in hepatocytes. Under inflammatory conditions, hepatocytes seem to weaken in the simultaneous administration of triglycerides and LPS, in contrast to the Kupffer cells, which potentiate the inflammatory response, the actual trend from inflammation. This manifests itself in a reduction of gene expression of proinflammatory mediators. However, hepatocytes accumulate intracellular triglycerides in the up-regulation, they are more susceptible to an inflammatory stimulus set. In contrast to the administration of triglycerides was the use of free fatty acid linoleic acid, a cytotoxic effect can be demonstrated. The datas of this study show that kill a high concentration of linoleic acid in particular, hepatocytes as well as to a somewhat lesser extent Kupffer cells. As already detected under triglyceride exposition, hepatocytes have also under the administration of linoleic acid in low concentrations more likely to move on to a reduced expression of proinflammatory mediators, so that it can be rather a protective effect. As well, under the administration of triglycerides, the datas show that Kupffer cells have under a simultaneous administration of linoleic acid in a low concentration of endotoxins, and significantly enhanced the induction of proinflammatory mediators in comparison to sole endotoxin treatment. The datas suggest that linoleic acid enhances the inflammatory response in Kupffer cells.