Gessani S, Di Marzio P, Baglioni C
Department of Virology, Istituto Superiore di Sanita, Roma, Italy.
J Interferon Res. 1989 Oct;9(5):543-50. doi: 10.1089/jir.1989.9.543.
Murine C127 fibroblasts carrying an expression vector for a human interferon gene (HuIFN-beta, under the control of a constitutive promoter) can be induced to produce murine (Mu) IFN by double-stranded (ds) RNA or virus infection. Fibroblasts treated with the protein kinase C activators 1-oleyl-2-acetylglycerol (OAG) or phorbol-12-myristate-13-acetate (PMA) secrete greater amounts of MuIFN than untreated cells, but the same amount of HuIFN-beta. Accordingly, the level of MuIFN-beta mRNA increases in the presence of protein kinase C activators whereas that of HuIFN-beta mRNA is unchanged. In time course experiments after induction with dsRNA, accumulation of MuIFN-beta mRNA is observed within 30 min in the presence of OAG, when this mRNA cannot be detected in control cells. The protein kinase C activators increase accumulation of MuIFN-beta mRNA, even in the presence of the inhibitor of protein synthesis cycloheximide. A similar increase in MuIFN-beta mRNA is observed in C243 fibroblasts treated with phorbol-12-myristate-13-acetate, but not in parental C127 cells. These findings suggest that protein kinase C does not promote synthesis of regulatory factors controlling transcription of IFN mRNA, but that it may be directly or indirectly involved in activation of such factors in some murine cell lines.
携带人干扰素基因(HuIFN-β,在组成型启动子控制下)表达载体的小鼠C127成纤维细胞可被双链(ds)RNA或病毒感染诱导产生小鼠(Mu)干扰素。用蛋白激酶C激活剂1-油酰-2-乙酰甘油(OAG)或佛波醇-12-肉豆蔻酸酯-13-乙酸酯(PMA)处理的成纤维细胞比未处理的细胞分泌更多的MuIFN,但HuIFN-β的分泌量相同。因此,在蛋白激酶C激活剂存在的情况下,MuIFN-β mRNA水平增加,而HuIFN-β mRNA水平不变。在用dsRNA诱导后的时间进程实验中,在OAG存在的情况下,30分钟内即可观察到MuIFN-β mRNA的积累,而在对照细胞中无法检测到这种mRNA。即使在存在蛋白质合成抑制剂环己酰亚胺的情况下,蛋白激酶C激活剂也会增加MuIFN-β mRNA的积累。在用佛波醇-12-肉豆蔻酸酯-13-乙酸酯处理的C243成纤维细胞中观察到MuIFN-β mRNA有类似的增加,但在亲代C127细胞中未观察到。这些发现表明,蛋白激酶C并不促进控制IFN mRNA转录的调节因子的合成,但在某些小鼠细胞系中,它可能直接或间接参与此类因子的激活。