Rat liver slices as a tool to study LPS-induced inflammatory response in the liver

Background/Aims: Inflammation in the liver is a complex interaction between parenchymal and non-parenchymal cells, and therefore can not be studied in vitro in pure cultures of these cells.

Methods: We investigated whether Kupffer cells in the liver slice are still responsive to an inflammatory stimulus of lipopolysaccharide (LPS), and evoke an inflammatory response in the hepatocytes.

Results: TNF alpha, IL-1 beta and IL-10 were significantly elevated in culture medium of LPS-stimulated rat liver slices. Nitric oxide (NO) production of LPS-treated slices gradually increased from 5 to 24 h (24 h: 81 +/- 5 muM vs. 14 +/- 2 muM in control P <0.05), paralleled by inducible nitric oxide synthase (iNOS) in the hepatocytes, iNOS mRNA was induced after 3 h. NO production but not iNOS induction was significantly inhibited by NOS inhibitors S-methylisothiourea and N-G-nitro-L-arginine methylester. Both pentoxifylline and dexamethasone inhibited TNF alpha and IL-1 beta production, albeit to a different extent, iNOS induction and, as a result thereof, NO production.

Conclusions: These results imply that non-parenchymal cells in liver slices are viable and can be activated by LPS. In addition, it is concluded that the upregulation of iNOS in hepatocytes by LPS is caused by cytokines produced by Kupffer cells because inhibition of TNF alpha and IL-1 beta production attenuated iNOS induction. (C) 2001 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.