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

Abstract：

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:TNFalpha, IL-1beta 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 microM vs. 14+/-2 microM 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 TNFalpha and IL-1beta 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 TNFalpha and IL-1beta production attenuated iNOS induction.

journal_name

J Hepatol

journal_title

Journal of hepatology

authors

Olinga P,Merema MT,de Jager MH,Derks F,Melgert BN,Moshage H,Slooff MJ,Meijer DK,Poelstra K,Groothuis GM

doi

10.1016/s0168-8278(01)00103-9

subject

Has Abstract

pub_date

2001-08-01 00:00:00

pages

187-94

issue

2

eissn

0168-8278

issn

1600-0641

pii

S0168-8278(01)00103-9

journal_volume

35

pub_type

杂志文章

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