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PKA对跨膜型和分泌型TNF |
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石文芳 李卓娅 龚非力 姜小丹 徐勇 熊平 冯玮
摘 要 目的：研究PKA对跨膜型TNF-α(mTNF-α)和分泌型TNF- α (TNF-α)杀瘤效应的影响。方法：用TNF生物活性检测方法在体外 观察PKA激活剂和抑制剂对二型TNF- α杀伤不同肿瘤细胞的影响。 结果：PKA激活剂Forskolin(10 μmol/L)和抑制剂H8(15 μmol/L) 可 分别增强和抑制sTNF-α对其敏感靶细胞的胞毒活性，对其余4株耐受靶细胞却无逆转作用 ，而且对mTNF-α的胞毒效应无任何影响。此外，PKA活性增强，可使sTNF-α介导靶细胞 的死亡方式发生改变，即坏死比例减少，凋亡比例增加。 结论：PKA仅参与sTNF-α胞毒作用的信号传导，与mTNF-α无关； 且与sTNF-α介导靶细胞凋亡有关。
关键词 肿瘤坏死因子-α 跨膜型 分泌型 细胞毒 坏死 凋 亡
中国图书分类号 R371-34
Effect of PKA on the cytotoxicity of transmembrane and secretory tumor necrosis factor-α
SHI Wen-Fang LI Zhuo-Ya GONG Fei-Li
（Department of Immunology,Tongji Medical University,Wuhan 430030）
Abstract Objective： To study the influe nce of PKA on the tumoricidal effect of transmembrane tumor necrosis factor-α( mTNF-α)and secretory TNF-α(sTNF-α). Methods: The effect of PKA activator and inhibi tor on the both forms of TNF-α was studied with TNF-α bioassay. Results:It was found that the activator(Forsko lin,10 μmol/L)of PKA potentiated,while its inhibitor(H8,15 μmol/L) depressed t he cytotoxic effect of sTNF-α on target cell lines sensitive to the cytokine.The se agents,however,were not capable of reversing the state of reactivity of the o ther four cell lines from tolerant to sensitive to sTNF-α,nor did it affect th e cytotoxicity of mTNF-α.Furthermore,increased activity of PKA was a reduced p roportion of necrosis and an increased one of apoptosis.Conclusion: PKA m ay be involved in the cytotoxic effect of sTNF-α rather than that of mTNF-α and may be associated with apoptosis induced by sTNF-α.
Key words Tumor necrosis factor-α Transmemb rane Secretory Cytotoxicity Necrosis Apoptosis
我们近来证实跨膜型TNF-α(transmembrane tumor necrosis factor-α,mTNF-α)比 分 泌型TNF-α(sTNF-α)有更广的杀瘤谱，即m[1] [2] [3] 下一页
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