Tamura-Nishimura M, Sasakawa S
Japanese Red Cross, Central Blood Center, Tokyo.
FEBS Lett. 1989 May 8;248(1-2):73-7. doi: 10.1016/0014-5793(89)80434-x.
The signal transduction mechanisms involved in interferon (IFN) gamma induction in human peripheral mononuclear lymphocyte nylon-nonadherent cells (NNA cells) by stimulation with poly(I):poly(C) are investigated. Significant enhancement of IFN gamma production by poly(I):poly(C) is observed in the presence of the phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA, a protein kinase C (PKC) activator). Our study shows that in NNA cells, poly(I):poly(C) with or without TPA causes prolonged activation of cytosolic PKC of NNA cells for at least 120 min. The level of activation of PKC is quite remarkable in the case of the combined stimulation by poly(I):poly(C) and TPA as compared to poly(I):poly(C) alone. This demonstrates that prolonged activation of cytosolic PKC for at least 120 min is essential for high levels of production of IFN gamma. Moreover, inhibition experiments using the PKC inhibitor H-7 and cAMP-dependent protein kinase inhibitor H-8 suggest that the mechanism of signal transduction with regard to PKC is involved in stimulation of IFN gamma production in NNA cells by poly(I):poly(C) in the presence of TPA and that along with PKC, cAMP-dependent protein kinase is probably involved in induction of IFN gamma by stimulation with poly(I):poly(C) alone.
聚胞苷酸（poly(I):poly(C)）刺激人外周血单个核淋巴细胞尼龙非黏附细胞（NNA细胞）时，参与γ干扰素（IFN）诱导的信号转导机制。在佛波酯12-O-十四酰佛波醇13-乙酸酯（TPA，一种蛋白激酶C（PKC）激活剂）存在的情况下，观察到poly(I):poly(C)显著增强了IFNγ的产生。我们的研究表明，在NNA细胞中，无论有无TPA，poly(I):poly(C)都会使NNA细胞的胞质PKC持续激活至少120分钟。与单独使用poly(I):poly(C)相比，poly(I):poly(C)和TPA联合刺激时PKC的激活水平相当显著。这表明胞质PKC持续激活至少120分钟对于高水平产生IFNγ至关重要。此外，使用PKC抑制剂H-7和环磷酸腺苷（cAMP）依赖性蛋白激酶抑制剂H-8的抑制实验表明，在TPA存在的情况下，关于PKC的信号转导机制参与了poly(I):poly(C)刺激NNA细胞产生IFNγ的过程，并且除了PKC之外，cAMP依赖性蛋白激酶可能也参与了单独使用poly(I):poly(C)刺激诱导IFNγ的过程。
