Potentiation by thyroxine of interferon-gamma-induced antiviral state requires PKA and PKC activities
Potentiation by thyroxine of interferon-gamma-induced antiviral state requires PKA and PKC activities
复制标题
DOI：
10.1152/ajpcell.1996.271.4.c1256
复制
发表时间：
1996-10-01
影响因子：
5.5
通讯作者：
Davis, PJ
中科院分区：
文献类型：
--
作者：
Lin, HY;Thacore, HR;Davis, PJ
将生理浓度的甲状腺激素[L-甲状腺素(T-4)]加入预先接触重组人干扰素-γ20h的HeLa细胞中，在4h内可使干扰素-γ的抗病毒作用增强100倍以上。我们检测了蛋白激酶活性，以探讨其在甲状腺激素翻译后效应机制中的作用。与甲状腺激素同时加入的蛋白激酶C(PKC)抑制剂CGP-41251(5 NM)可阻断T-4对干扰素-γ作用的增强。佛波醇12-肉豆蔻酸酯(PA)与CGP-41251共同孵育后，可逆转抑制剂对甲状腺激素作用的影响。磷脂酶C抑制剂U-73122(10 NM)也可阻断激素的增强作用。蛋白激酶A(PKA)抑制剂KT-5720(500 NM)可完全抑制T-4效应，而8-溴腺苷3‘，5’-环一磷酸(8-BrcAMP)可恢复KT-5720的激素作用。在没有T-4的情况下，8-BrcAMP和PMA一起加入细胞中，在4-h范式中，完全复制了激素增强的干扰素-γ的抗病毒作用。两种激动剂单独与干扰素-γ处理的细胞孵育后，没有增强作用。甲状腺激素显然必须激活非基因组途径中的PKA和PKC，以增强HeLa细胞的抗病毒活性。
Added to HeLa cells previously exposed to recombinant human interferon (IFN)-gamma for 20 h, thyroid hormone [L-thyroxine (T-4)] in physiological concentrations potentiates the antiviral action of IFN-gamma by more than 100-fold in 4 h. We examined protein kinase activities for their contributions to the mechanism of this posttranslational effect of thyroid hormone. Added concurrently with thyroid hormone, the protein kinase C (PKC) inhibitor CGP-41251 (5 nM) blocked T-4 potentiation of IFN-gamma action. Coincubated with CGP-41251, phorbol 12-myristate 13-acetate (PA) reversed the effect of the inhibitor on thyroid hormone action. U-73122 (10 nM), a phospholipase C inhibitor, also blocked hormone potentiation. KT-5720 (500 nM), a protein kinase A (PKA) inhibitor, completely inhibited the T-4 effect, whereas 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) restored hormone action in the presence of KT-5720. In the absence of T-4, 8-BrcAMP and PMA, added together to cells in the 4-h paradigm, fully reproduced hormone potentiation of the antiviral effect of IFN-gamma. Incubated individually with IFN-gamma-treated cells, the two agonists had no potentiating action. Thyroid hormone apparently must activate both PKA and PKC in the nongenomic pathway of IFN-gamma action to enhance antiviral activity in HeLa cells.