Involvement of nuclear binding sites for melatonin in the regulation of IL-2 and IL-6 production by human blood mononuclear cells
Involvement of nuclear binding sites for melatonin in the regulation of IL-2 and IL-6 production by human blood mononuclear cells
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DOI：
10.1016/s0165-5728(98)00179-9
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发表时间：
1998-12-01
影响因子：
3.3
通讯作者：
Guerrero, JM
中科院分区：
文献类型：
--
作者：
Garcia-Mauriño, S;Gonzalez-Haba, MG;Guerrero, JM
许多功能研究表明，褪黑激素在神经免疫调节中起着重要作用。在本文中，我们已经扩展了我们的研究的影响，褪黑激素对IL-2和IL-6的生产由人外周血单核细胞（PBMC）的特异性膜受体激动剂S 20098，RZR/ROR α受体激动剂CGP 52608，和结构相关的噻唑烷二酮类药物的效果进行了比较。褪黑激素以大约相同的亲和力（IC，值约5 nM）结合到人PBMC的膜以及细胞核。S 20098与PBMC膜结合，但不与PBMC核结合，尽管亲和力比褪黑激素低至少100倍;该化合物不刺激细胞因子产生。相比之下，所有四种CGP化合物都不与PBMC膜结合，而与细胞核的结合表现出ICS值，与褪黑激素的值相当。激活RZR/ROR α受体的噻唑烷二酮类（CGP 52608，CGP 53079）也增加了IL-2和IL-6的产生。CGP 55644对IL-2和IL-6的产生无影响，但能拮抗CGP 52608对IL-2和IL-6产生的影响，并能降低褪黑素引起的IL-2的产生。在单核细胞培养物中获得的结果与PBMC中显示的结果非常相似。本文报道的结果证实了褪黑激素对人PBMC中细胞因子产生的影响涉及核机制。我们还显示了S 20098和CGP 52608的协同作用，表明PBMC中核和膜褪黑激素受体之间可能存在联系。(C)1998 Elsevier Science B. V.保留所有权利。
Many functional studies show that melatonin plays a fundamental role in neuroimmunomodulation. In this paper, we have extended our studies on the influence of melatonin on IL-2 and IL-6 production by human peripheral blood mononuclear cells (PBMCs) by comparing the effects of the specific membrane receptor agonist S 20098, the RZR/RORalpha receptor agonist CGP 52608, and structurally related thiazolidinediones. Melatonin bound to membranes as well as to nuclei of human PBMCs with about the same affinity (IC,, values around 5 nM). S 20098 bound to PBMC membranes but not to PBMC nuclei, although the affinity was at least 100 times lower than that of melatonin; this compound did not stimulate cytokine production. In contrast, all four CGP compounds did not bind to PBMC membranes, while binding to nuclei exhibited ICS, values comparable to those of melatonin. The thiazolidinediones activating the RZR/RORalpha receptor (CGP 52608, CGP 53079) also increased IL-2 and IL-6 production. CGP 55644 had no effect on cytokine production and antagonized the effects of CGP 52608 on IL-2 and IL-6 production; moreover, CGP 55644 decreased the enhanced IL-2 production caused by melatonin. Results obtained in monocyte cultures resembled closely those shown in PBMCs. The results reported in this paper confirm the involvement of a nuclear mechanism in the melatonin effects on cytokine production in human PBMCs. We have also shown a synergistic effect of S 20098 and CGP 52608, suggesting a possible link between nuclear and membrane melatonin receptors in PBMCs. (C) 1998 Elsevier Science B.V. All rights reserved.