Effects of Kupffer cell inhibition on liver function and hepatocellular activity in mice.

Published on Oct 1, 2003in International Journal of Molecular Medicine3.098
· DOI :10.3892/IJMM.12.4.549
Hong Ding1
Estimated H-index: 1
(WHU: Wuhan University),
Renxiu Peng1
Estimated H-index: 1
+ 1 AuthorsQingdi Q. Li18
Estimated H-index: 18
Sources
Abstract
Kupffer cells are the tissue macrophages in the liver and play an important role in the defense mechanisms of the body. However, their role in liver function and hepatocellular activity remains unclear. This study was therefore undertaken to investigate the effect of gadolinium chloride-induced Kupffer cell dysfunction on liver function and hepatocellular signaling activity in mice and to establish an animal model for studying the role of Kupffer cells in vivo. Kunming mice were intraperitoneally injected with different doses of gadolinium chloride (GdCl 3 ), a selective inhibitor of Kupffer cells, and the mice were sacrificed at different time periods following the drug administration. Hepatotoxicity and Kupffer cell function, as well as the levels of signaling molecules and inflammatory mediators in liver tissue, were measured. We demonstrated that the administration of 10-20 mg/kg GdCl 3 caused apoptosis of Kupffer cells and blocked the Kupffer cell effector function, as shown by a decrease in CD68 expression and phagocytic activity. In addition, the NO, PGE 2 and cAMP levels in the liver were also reduced significantly. Furthermore, 20 mg/kg GdCl 3 decreased the levels of cNOS, PKC and NF-KB p65 expression by 26.6, 68 and 64%, respectively. In contrast, hepatotoxicity was not observed when the same doses of GdCl 3 were used. Moreover, we found that Kupffer cell function and the NO, PGE 2 and cAMP contents, as well as PKC and NF-κB p65 levels in the liver were only partially, but not fully recovered in up to six days following 20 mg/kg GdCl 3 injection. However, the administration of higher doses of GdCl 3 (40 mg/kg) caused both hepatotoxicity and Kupffer cell necrosis, as well as an increased release of TNF, NO, and PGE 2 in the liver. These results indicate that administration of suitable doses of GdCl 3 blocked the effector function of Kupffer cells selectively, but did not cause liver parenchymal cell toxicity, and provide a frame-work for the establishment of an animal model for studying the role of Kupffer cells in signaling in the liver. Lastly, the present study also provides evidence that shows there is a positive association between the expression of cAMP, PKC, or NF-KB and the levels of NO, PGE 2 and TNF in the liver of Kupffer-cell-blocked mice, and suggests that Kupffer cells may play a part in mediating liver function and hepatocellular activity.
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