Augmented regeneration of partial liver allograft induced by nuclear factor-kB decoy oligodeoxynucleotides-modified dendritic cells

被引:4
作者
Ming-Qing Xu Yu-Ping Suo Jian-Ping Gong Ming-Man Zhang Lü-Nan Yan Department of General Surgery
机构
关键词
gene; NF; Augmented regeneration of partial liver allograft induced by nuclear factor-kB decoy oligodeoxynucleotides-modified dendritic cells;
D O I
暂无
中图分类号
R657.3 [肝及肝管];
学科分类号
1002 ; 100210 ;
摘要
AIM:To investigate the effect of NF-κB decoyoligodeoxynuleotides(ODNs)-modified dendritic cells(DCs)on regeneration of partial liver allograft.METHODS:Bone marrow(BM)-derived DCs from SD ratswere propagated in the presence of GM-CSF or GM-CSF+IL-4 to obtain immature DCs or mature DCs,respectively.GM-CSF-propagated DCs were treated with double-strand NF-~Bdecoy ODNs containing two NF-κB binding sites or scrambledODNs.Allogeneic(SD rat to LEW rat)50% partial livertransplantation was performed.Normal saline(group A),GM-CSF-propagated DCs(group B),GM-CSF+IL-4-propagated DCs(group C),and GM-CSF+NF-κB decoy ODNs(group D)or scrambled ODNs-propagated DCs(group E)were injected intravenously into recipient LEW rats 7 daysprior to liver transplantation and immediately aftertransplantation.DNA synthesis(BrdU labeling)and apoptosisof hepatocytes were detected with immunostaining andTUNEL staining postoperative 24 h,48 h,72 h and 84 h,respectively.Liver graft-resident NK cell activity,hepaticIFN-γ mRNA expression and recipient serum IFN-γ level atthe time of the maximal liver allograft regeneration weremeasured with51Cr release assay,semiquantitative RT-PCRand ELISA,respectively.RESULTS:Regeneration of liver allograft was markedlypromoted by NF-κB decoy ODNs-modified immature DCsbut was significantly suppressed by mature DCs,the DNAsynthesis of hepatocytes peaked at postoperative 72 h ingroup A,group B and group E rats,whereas the DNAsynthesis of hepatocytes peaked at postoperative 84 h ingroup C rats and 48 h in group D rats,respectively.Themaximal BrdU labeling index of hepatocytes in group D ratswas significantly higher than that in the other groups rats.NF-κB decoy ODNs-modified immature DCs markedlysuppressed but mature DCs markedly promoted apoptosisof hepatocytes,liver-resident NK cell activity,hepatic IFN~mRNA expression and recipient serum IFN-γ production.Atthe time of the maximal regeneration of liver allograft,theminimal apoptosis of hepatocytes,the minimal activity ofliver-resident NK cells,the minimal hepatic IFN-γ mRNAexpression and serum IFN-γ production were detected ingroup D rats.The apoptotic index of hepatooltes,the activity of liver-resident NK cells,the hepatic IFN-γ mRNA expressionlevel and the serum IFN-γ level in group D rats were significantlylower than that in the other groups rats at the time of themaximal regeneration of liver allograft.CONCLUSION:The data suggest that the augmentedregeneration of partial liver allograft induced by NF-κB decoyODNs-modified DCs may be attributable to the reducedapoptotic hepatocytes,the suppressed activity of liver-resident NK cells and the reduced IFN-γ production.
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页码:573 / 578
页数:6
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