Inhibition by chlorpromazine of lymphokine-specific mRNA expression in human thymocytes.
Inhibition by chlorpromazine of lymphokine-specific mRNA expression in human thymocytes.
复制标题
氯丙嗪抑制人胸腺细胞中淋巴因子特异性 mRNA 的表达。
DOI：
10.1002/eji.1830190822
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发表时间：
1989
影响因子：
5.4
通讯作者：
Reem,GH
中科院分区：
文献类型：
--
作者：
Schleuning,MJ;Duggan,A;Reem,GH
本研究旨在确定吩噻嗪氯丙嗪（CPZ）对人胸腺细胞活化的影响。我们提供的证据表明，CPZ抑制淋巴因子白细胞介素2、干扰素-γ、肿瘤坏死因子α和原癌基因c-myc特异性mRNA的蓄积;相反，CPZ不抑制白细胞介素2受体α链特异性mRNA的蓄积和随后细胞表面Tac抗原的早期表达。通过[3 H]胸苷掺入测定，淋巴因子特异性mRNA表达的抑制导致γ-干扰素合成减少和胸腺细胞增殖抑制。此外，我们发现，12-O-十四酰基佛波醇13-乙酸酯（TPA）激活人胸腺细胞中的蛋白激酶C（PKC），导致分子量约为75 kDa的蛋白质磷酸化。这种蛋白的功能尚未确定，但它可能在将信号转导到细胞核中起作用，而细胞核又引起编码c-myc和胸腺细胞活化所需的淋巴因子的基因的表达。我们还证明，CPZ，像免疫抑制剂药物环孢素A不抑制磷酸化的75 kDa蛋白，这是由TPA激活PKC诱导的，不影响磷酸肌醇分解，表明它发挥其作用的网站远端的PKC的激活。这些观察结果表明，CPZ具有免疫调节功能，除了其精神活性。
This study was designed to determine the effect of the phenothiazine chlorpromazine (CPZ) on the activation of human thymocytes. We provide evidence that CPZ inhibits the accumulation of mRNA specific for the lymphokines interleukin 2, interferon‐γ, tumor necrosis factor α and the proto‐oncogene c‐myc; by contrast, the accumulation of mRNA specific for the α chain of the interleukin 2 receptor and the subsequent early expression of Tac antigen on the cell surface is not inhibited by CPZ. The inhibition of the expression of lymphokine‐specific mRNA results in a decrease in interferon‐γ synthesis and in inhibition of thymocyte proliferation as determined by the incorporation of [3H]thymidine. In addition, we show that activation of protein kinase C (PKC) in human thymocytes by 12‐O‐tetradecanoyl phorbol 13‐acetate (TPA) causes the phosphorylation of a protein of a molecular mass of approximately 75 kDa. The function of this protein is as yet not defined, but it is possible that it plays a role in the transduction of the signals to the nucleus which in turn elicit the expression of the genes coding for c‐myc and for the lymphokines required for thymocyte activation. We also demonstrate that CPZ, like the immunosuppressant drug cyclosporin A does not inhibit the phosphorylation of the 75‐kDa protein which is induced by the activation of PKC by TPA and does not affect phosphoinositide breakdown, indicating that it exerts its effect at a site distal to the activation of PKC. These observations demonstrate that CPZ has an immunoregulatory function in addition to its psychotropic activity.