Abstract
Hepatic macrophages have the capacity to secrete a tremendous array of molecules, which can be divided into 3 categories e cytokines (TNF-alpha), lipid mediators (prostaglandins PGE2) and reactive intermediates (NOe) e in response to stimulus, such as lipopolysaccharides (LPS) [1,2]. Such mediators are capable to modulate both the metabolism and the integrity of hepatocytes in vitro [2]. The physiological role of Kupffer cell in hepatic metabolism regulation has been approached in the present study by using the original in vitro model of precision-cut liver slices (PCLS) in culture; this model allows preserving the liver lobule architecture, by maintaining namely cell diversity in physiological proportion and cell-cell interactions [3]. First, we established whether non-parenchymal cells are still viable in rat PCLS and are able to respond to LPS in vitro; TNF-alpha, PGE2, NOx (reflecting NOe release) were measured in the incubation medium of PCLS from rats previously treated with GdCl3 e a specific inhibitor of Kupffer cell phagocytosis [4] e or NaCl as a control- in order to evaluate the contribution of Kupffer cell in mediator release. Moreover, by using the same model, we have investigated the role of Kupffer cell in the regulation of lipid synthesis in PCLS, in order to approach the biochemical mechanism explaining our last results, which indicate that the inhibition of Kupffer cell by GdCl3 leads to triglycerides accumulation in liver tissue [5].
Highlights
Hepatic macrophages have the capacity to secrete a tremendous array of molecules, which can be divided into 3 categories – cytokines (TNF-alpha), lipid mediators and reactive intermediates (NO·) – in response to stimulus, such as lipopolysaccharides (LPS) [1,2]
We established whether non-parenchymal cells are still viable in rat precision-cut liver slices (PCLS) and are able to respond to LPS in vitro; TNF-alpha, PGE2, NOx were measured in the incubation medium of PCLS from rats previously treated with GdCl3 – a specific inhibitor of Kupffer cell phagocytosis [4] – or NaCl as a control- in order to evaluate the contribution of Kupffer cell in mediator release
Validation of the PCLS model to assess the functionality of Kupffer cells Unstimulated-PCLS in culture release in the medium significant amount of TNF-alpha, PGE2 and NOx (Figure 1) which level increases with the time of incubation
Summary
Hepatic macrophages have the capacity to secrete a tremendous array of molecules, which can be divided into 3 categories – cytokines (TNF-alpha), lipid mediators (prostaglandins PGE2) and reactive intermediates (NO·) – in response to stimulus, such as lipopolysaccharides (LPS) [1,2]. Such mediators are capable to modulate both the metabolism and the integrity of hepatocytes in vitro [2]. By using the same model, we have investigated the role of Kupffer cell in the regulation of lipid synthesis in PCLS, in order to approach the biochemical mechanism explaining our last results, which indicate that the inhibition of Kupffer cell by GdCl3 leads to triglycerides accumulation in liver tissue [5]
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