Effects of anti-proliferative cyclic AMP on interleukin 2-stimulated gene expression.

Effects of anti-proliferative cyclic AMP on interleukin 2-stimulated gene expression.
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抗增殖环 AMP 对白细胞介素 2 刺激的基因表达的影响。

DOI:
10.4049/jimmunol.139.6.2075
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发表时间:
1987
影响因子:
4.4
通讯作者:
J. Cleveland
J. Cleveland
中科院分区:
医学2区
文献类型:
--
作者:
W. Farrar;S. Evans;U. Rapp;J. Cleveland

文献摘要

被引文献

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升高细胞内环腺苷3′:5′单磷酸(cAMP)抑制白细胞介素2 (IL-2)刺激的小鼠细胞毒性细胞克隆CT6的增殖。研究了稳定的camp衍生物8-溴腺苷3′:5′-单磷酸(8-Br-cAMP)抗增殖剂量对IL-2刺激的稳态mRNA表达的影响。IL-2刺激三种核原癌基因c-fos、c-myc和c-myb的mRNA积累。通过Northern blot分析,8-Br-cAMP单独刺激c-fos、c-myb和IL-2受体mRNA的积累。然而,8-Br-cAMP明显抑制IL-2刺激的c-myc表达。此外,虽然8-Br-cAMP增强了c-fos和IL-2受体mRNA的表达,但也抑制了蛋白质的合成。我们发现,除c-myc外,抗增殖性cAMP刺激与IL-2相似的mRNA表达。虽然一些基因的稳态mRNA积累发生了比较刺激,但cAMP可能对蛋白质合成产生深远影响。因此,cAMP作用于参与IL-2刺激的大分子事件的多个靶点。
Elevation of intracellular cyclic adenosine 3':5' monophosphate (cAMP) inhibits interleukin 2 (IL-2)-stimulated proliferation of a murine cytotoxic cell clone, CT6. The effects of antiproliferative dosages of stable cAMP-derivative, 8-bromoadenosine 3':5'-monophosphate (8-Br-cAMP), on steady state mRNA expression stimulated by IL-2 was examined. IL-2 stimulated mRNA accumulation of three nuclear proto-oncogenes c-fos, c-myc, and c-myb. 8-Br-cAMP alone stimulated c-fos, c-myb, and IL-2 receptor mRNA accumulation as determined by Northern blot analysis. 8-Br-cAMP, however, markedly inhibited c-myc expression stimulated by IL-2. Furthermore, although c-fos and IL-2 receptor mRNA expression was potentiated by 8-Br-cAMP, suppression of protein synthesis was seen. We show that antiproliferative cAMP stimulates similar mRNA expression as does IL-2, with the exception of c-myc. Although a comparative stimulation of steady state mRNA accumulation of some genes occurs, cAMP may profoundly effect protein synthesis. cAMP, therefore, acts on multiple targets involved in the macromolecular events stimulated by IL-2.