PKA对跨膜型和分泌型TNF-α胞毒效应的影响

Effect of PKA on the cytotoxicity of transmembrane and secretory tumor necrosis factor-α

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

Objective: To study the influence 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 inhibitor on the both forms of TNF α was studied with TNF α bioassay. Results:It was found that the activator(Forskolin,10 μmol/L)of PKA potentiated,while its inhibitor(H8,15 μmol/L) depressed the cytotoxic effect of sTNF α on target cell lines sensitive to the cytokine.These agents,however,were not capable of reversing the state of reactivity of the other four cell lines from tolerant to sensitive to sTNF α,nor did it affect the cytotoxicity of mTNF α.Furthermore,increased activity of PKA was a reduced proportion of necrosis and an increased one of apoptosis.Conclusion: PKA may 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.