Interleukin-18 antisense oligodeoxynucleotide promotes hepatocyte regeneration of partial liver allograft.
- Author:
Ming-qing XU
1
;
Zhen-xiang YAO
;
Lan XUE
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Hepatocytes; physiology; Interferon-gamma; biosynthesis; Interleukin-18; antagonists & inhibitors; genetics; Liver Regeneration; Male; Oligodeoxyribonucleotides, Antisense; pharmacology; Rats; Rats, Inbred Lew; Rats, Sprague-Dawley; Transplantation, Homologous
- From: Chinese Journal of Hepatology 2004;12(1):40-43
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo study the effect of interleukin (IL)-18 ASPODN on regeneration of allogeneic partial liver graft in rats.
METHODSNinety donor SD rats and ninety recipient LEW rats were randomly divided into 3 groups: 50% partial liver transplantation group (PLT group); PLT+IL-18 antisense phosphorothioate oligodeoxynucleotide (ASPODN) treatment group (IL-18 ASPODN group) and PLT+IL-18 SPODN treatment group (IL-18 SPODN group) in which liposomes encapsulated IL-18 ASPODN or IL-18 SPODN were intravenous injection every day after PLT. BrdU labeling of hepatocytes, expression of IL-18 protein and IFN-gamma mRNA in liver graft, and serum level of IFN-gamma were measured with immunohistochemistry analysis, Western blotting, semi-quantification RT-PCR, and ELISA, respectively.
RESULTSAlthough regeneration of liver graft from each group peaked 72 hour after transplantation, BrdU labeling of hepatocytes in IL-18 ASPODN group (58.3%+/-7.5%) were significantly higher than those of PLT group (31.6%+/-6.7%) (t=6.503, P<0.001) and IL-18 SPODN group (33.4%+/-5.5%) (t=6.558, P<0.001). Expression of IL-18 protein and IFN-gamma mRNA in liver graft, and serum level of IFN-gamma in IL-18 ASPODN group from 48 hour, 72 hour and 96 hour after transplantation were significantly suppressed compared with PLT group (IL-18protein: t=2.950, t=5.916, t=7.947, P<0.05, P<0.001; INF-gamma mRNA: t=2.558, t=6.292, t=8.925, P<0.05, P<0.001; IFN-gamma level: t=16.998, t=15.483, t=54.723, P<0.001) and IL-18 SPODN group (IL-18 protein: t=2.845, t=6.062, t=6.973, P<0.05, P<0.001; INF-gamma mRNA: t=3.117, t=6.154, t=8.738, P<0.05, P<0.001; IFN-gamma level: t=14.531, t=18.139, t=46.924, P<0.001).
CONCLUSIONIL-18 ASPODN could promote hepatocyte regeneration of allogeneic partial liver graft by the suppression of IL-18 and IFN-gamma production.
