Hahn S, Moroni C
Institute for Medical Microbiology, University of Basel, Switzerland.
Lymphokine Cytokine Res. 1994 Aug;13(4):247-52.
Stimulation of mast cells, either via the IgE receptor or with calcium ionophore triggers the production of several cytokines, such as interleukins-3, -4, -5, and -6, and GM-CSF. In PB-3c mastocytes, ionophore-induced IL-3 and GM-CSF expression is primarily the result of mRNA stabilization, and is enhanced by oncogenic ras. Apart from mobilizing calcium, the IgE receptor activation leads to production of DAG and elevation of cAMP levels, thereby activating protein kinases C and A, respectively. The influence of these two secondary messengers on cytokine production was examined using the cAMP elevating agent IBMX, the phorbol ester PMA, and the staurosporine derivative CGP 41251, which preferentially inactivates PKC. IBMX was determined to be a potent coinducer of IL-3 expression, whereas elevation of IL-6 and GM-CSF was more pronounced in PMA-treated cells. Both PMA and IBMX were shown to act posttranscriptionally on IL-3, by extending the half-life of the mRNA. Ionophore-induced cytokine expression appears to require serine/threonine kinase activity, as it could be abolished by treatment with the drug CGP 41251. Our results therefore suggest that the factors regulating cytokine expression and mRNA stability are subject to regulation by serine/threonine phosphorylation.
通过IgE受体或钙离子载体刺激肥大细胞会触发多种细胞因子的产生，如白细胞介素-3、-4、-5和-6以及粒细胞-巨噬细胞集落刺激因子（GM-CSF）。在PB-3c肥大细胞中，离子载体诱导的IL-3和GM-CSF表达主要是mRNA稳定化的结果，并被致癌性ras增强。除了动员钙离子外，IgE受体激活还会导致二酰基甘油（DAG）的产生和cAMP水平的升高，从而分别激活蛋白激酶C和A。使用cAMP升高剂异丁基甲基黄嘌呤（IBMX）、佛波酯PMA和优先使蛋白激酶C（PKC）失活的星形孢菌素衍生物CGP 41251研究了这两种第二信使对细胞因子产生的影响。已确定IBMX是IL-3表达的有效共诱导剂，而在PMA处理的细胞中IL-6和GM-CSF的升高更为明显。PMA和IBMX都通过延长mRNA的半衰期在转录后作用于IL-3。离子载体诱导的细胞因子表达似乎需要丝氨酸/苏氨酸激酶活性，因为用药物CGP 41251处理可以消除这种表达。因此，我们的结果表明，调节细胞因子表达和mRNA稳定性的因素受丝氨酸/苏氨酸磷酸化的调控。
