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

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.