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IFN-γ对TRAIL诱导HBV相关性肝癌细胞凋亡的调节作用 被引量:5

The effect of IFN-γ on TRAIL-induced apoptosis in HBV related hepatocarcinoma cell line
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摘要 目的 以转染了HBV全基因组、并稳定表达HBV病毒颗粒的HepG2 .2 .15细胞为细胞模型 ,探讨IFN γ对新型凋亡分子TRAIL(TNF相关的诱导凋亡配体 )诱导凋亡的影响 ,并初步探索其发生机制。方法 以流式细胞仪检测IFN γ和TRAIL作用前后 ,HepG2 .2 .15细胞的凋亡率。分别用流式细胞术和半定量RT PCR的方法检测IFN γ作用 0、6、12和 2 4h后 ,细胞表面膜结合型TRAIL和TRAIL受体mRNA的表达。用HBsAg和HBeAgELISA检测试剂盒测定IFN γ作用 0、6、12和 2 4h后 ,HBV病毒颗粒的分泌表达状况。结果 TRAIL单独作用、IFN γ单独作用、TRAIL和IFN γ联合作用后 ,HepG2 .2 .15细胞的凋亡率分别为 9.12 %、5 .84%和 46 .6 8% ,表明IFN γ可以显著上调TRAIL诱导的细胞凋亡。IFN γ作用后 ,细胞表面膜型TRAIL的表达有显著上调 ,而部分与TRAIL诱导凋亡相关的TRAIL受体的表达也有不同程度的上调 ,并且IFN γ可以抑制HepG2 .2 .15细胞HBV病毒颗粒的分泌。结论 转染HBV全基因组的HepG2 .2 .15细胞对TRAIL诱导的凋亡相对耐受 ,而IFN γ却可以逆转这种耐受 ,使其变得对TRAIL诱导的凋亡敏感。其发生机制可能是通过IFN γ上调细胞表面TRAIL及其受体的表达 ,以及抑制HBV病毒颗粒的分泌实现的。 Objective To explore the influence of IFN-γ on TRAIL (TNF related apoptosis inducing ligand)-induced apoptosis. Methods Apoptosis induced by TRAIL, IFN-γ, TRAIL plus IFN-γ was detected by flowcytometry, respectively. The expressions of membrane-bound TRAIL and its receptors were detected by flowcytometry and semi-quantitive RT-PCR respectively. The HBV particles secreted by HepG2.2.15 were detected by HBsAg and HBeAg detecting ELISA kit. Results HepG2.2.15 cell line was relatively resistant to TRAIL-induced apoptosis, but it could be made sensitive to TRAIL-induced apoptosis by IFN-γ (9.12% vesus 46.68%, P<0.01). The expression of TRAIL and some of its receptors was upregulated by IFN-γ. The amount of secreted HBV particles was decresed by IFN-γ. Conclusion IFN-γ can sensitive HepG2.2.15 cells to TRAIL-induced apoptosis to a great extent and this may be realized by the upregulated expression of TRAIL and some of its receptors and the decreased secretion of the HBV particles. [
出处 《中华微生物学和免疫学杂志》 CAS CSCD 北大核心 2003年第1期34-37,共4页 Chinese Journal of Microbiology and Immunology
基金 国家自然科学基金委海外青年学者合作研究基金资助项目 ( 30 12 80 2 3) 国家自然科学基金资助项目 ( 30 0 70 341)
关键词 IFN-Γ TRAIL HBV 肝癌 细胞凋亡 调节作用 TRAIL Hepatitis B virus IFN-γ Apoptosis
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参考文献9

  • 1Sheridan JP;Marsters SA;Pitti RM.Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors[J],1997(5327).
  • 2韩丽辉,孙汶生,马春红,张利宁,曹英林,宋静,陈有海.乙型肝炎病毒对肿瘤坏死因子相关的凋亡诱导配体诱导凋亡的影响及其机制[J].中华医学杂志,2002,82(9):597-600. 被引量:6
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二级参考文献7

  • 1Sheridan JP;Marsters SA;Pitti RM.Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors[J],1997(5327).
  • 2Thomas SG;Wilson AC;Glenn CJ.Intercellular regulation of TRAIL-induced apoptosis in human melanoma cells,1998.
  • 3Schneider P;Holler N;Bodmer JL.Conversion of membrane-bound fas(CD95) ligand to its soluble form is associated with downregulation of its proapoptotic activity and loss of liver toxicity[J],1998.
  • 4David JP;Toshiaki M;Toshimitsu S.Phosphatidylinositol 3-kinase/Akt activity regulates c-FLIP expression in tumor cells[J],2001.
  • 5Wiley SR;Schooley K;Smolak PJ.Identification and characterization of new member of the TNF family that induces apoptosis[J],1995.
  • 6Schneider P;Tschopp J.Apoptosis induced by death receptors[J],2000(2/3).
  • 7Leverkus M;Neumann M;Mengling T.Regulation of tumor necrosis factor-related apoptosis-inducing ligand sensitivity in primary and transformed human keratinocytes[J],2000.

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