Morphine inhibits transcriptional activation of IL-2 in mouse thymocytes
Morphine inhibits transcriptional activation of IL-2 in mouse thymocytes
复制标题
DOI：
10.1006/cimm.1997.1147
复制
发表时间：
1997-07-10
影响因子：
4.3
通讯作者：
Barke, RA
中科院分区：
文献类型：
--
作者：
Roy, S;Chapin, RB;Barke, RA
长期用吗啡治疗小鼠会影响免疫细胞的增殖、分化和功能。在本研究中，我们研究了吗啡抑制植物血凝素(PHA)/白细胞介素-1 （IL-1）诱导的胸腺细胞增殖的机制。与对照培养物相比，吗啡处理的胸腺细胞显示出生物活性IL-2和IL-2 mRNA的稳态水平降低。通过核径流测定，IL-2浓度的降低和转录物水平的降低与IL-2 mRNA合成速率的降低密切相关。随后的研究表明，吗啡治疗通过抑制特异性反式激活核因子c-Fos的合成来影响IL-2启动子的转录控制元件。半定量RT-PCR检测的c-Fos mRNA水平在吗啡治疗和PHA和IL-1激活后显著降低。在相同的条件下，c-Jun mRNA水平没有改变。用AP-1一致寡核苷酸进行的电泳迁移研究表明，吗啡处理的细胞制备的核提取物中AP-1蛋白复合物的形成水平显著降低。这些研究首次证明阿片类生物碱如吗啡可以通过干扰IL-2基因的转录激活来损害丝裂原淋巴因子激活的胸腺细胞增殖。(C) 1997学术出版社。
Chronic treatment of mice with morphine affects the proliferation, differentiation, and function of immune cells. In the present study, we investigated the mechanism by which morphine inhibits phytohemagglutinin (PHA)/interleukin-1 (IL-1)-induced thymocyte proliferation. When compared to control cultures, morphine-treated thymocytes showed decreased steady-state levels of bioactive IL-2 and IL-2 mRNA. The reduced IL-2 concentration and reduced transcript levels correlated well with a decreased rate of synthesis of IL-2 mRNA as determined by nuclear runoff assays. Subsequent studies showed that morphine treatment affected transcriptional control elements of the IL-2 promoter by inhibiting the synthesis of a specific trans-activating nuclear factor, c-Fos. c-Fos mRNA levels measured by semiquantitative RT-PCR were significantly decreased in thymocytes following treatment with morphine and activation with PHA and IL-1. Under identical conditions, c-Jun mRNA levels were not altered. Electrophoretic mobility shift studies with the AP-1 consensus oligonucleotide showed significantly decreased levels of AP-1-protein complex formation in nuclear extracts prepared hom morphine-treated cells. These studies demonstrate for the first time that opioid alkaloids such as morphine can impair mitogen-lymphokine-activated thymocyte proliferation by interfering with transcriptional activation of the IL-2 gene. (C) 1997 Academic Press.