Melatonin counteracts the inhibitory effect of PGE2 on IL-2 production in human lymphocytes via its mt1 membrane receptor
Melatonin counteracts the inhibitory effect of PGE2 on IL-2 production in human lymphocytes via its mt1 membrane receptor
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DOI：
10.1096/fj.02-0501fje
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发表时间：
2003-02-01
期刊：
影响因子：
4.8
通讯作者：
Guerrero, JM
中科院分区：
文献类型：
--
作者：
Carrillo-Vico, A;García-Mauriño, S;Guerrero, JM
众所周知，褪黑激素在人类神经免疫调节中起着重要作用。因此，褪黑激素调节大量细胞因子的产生，包括人类系统中的白细胞介素-2（IL-2）。褪黑激素的膜受体和核受体都存在于淋巴细胞中。然而，大多数这些作用已被证明是由神经激素的假定核受体介导的。在本文中，我们表明前列腺素E-2（PGE（2）），一种强有力的炎症介质，抑制IL-2的产生在人类淋巴细胞通过环磷酸腺苷（cAMP）依赖性机制。在这个模型中，褪黑激素抵消了PGE（2）对IL-2和cAMP产生的影响。我们建议，褪黑激素的效果是由膜受体介导的，因为类似的结果时，细胞培养在S 20098，一个特定的褪黑激素膜受体激动剂的存在下。使用核受体激动剂CGP 52608没有观察到效果。此外，当用佛波醇肉豆蔻酸酯乙酸酯（PMA）刺激细胞时，这种神经激素不能抵消PGE的作用（2），佛波醇肉豆蔻酸酯乙酸酯（PMA）已被证明能抑制mt1褪黑激素膜受体的表达。因此，我们假设，第一次，在人类免疫系统中的MT 1褪黑激素膜受体的生理作用。
It is well known that melatonin plays a fundamental role in human neuro-immunomodulation. Thus, melatonin regulates the production of a large number of cytokines, including interleukin-2 (IL-2) in the human system. Both membrane and nuclear receptors for melatonin are present in lymphoid cells. However, most of these effects have been shown to be mediated by the putative nuclear receptor for the neurohormone. In this paper, we show that prostaglandin E-2 (PGE(2)), a potent inflammatory mediator, inhibits IL-2 production in human lymphocytes by a cyclic AMP (cAMP)-dependent mechanism. In this model, melatonin counteracts the effects of PGE(2) on IL-2 and cAMP production. We propose that the effect of melatonin is mediated by a membrane receptor, since similar results were obtained when cells were cultured in the presence of S 20098, a specific melatonin membrane receptor agonist. No effect was observed by using CGP 52608, a nuclear receptor agonist. Moreover, when cells were stimulated with phorbol myristate acetate (PMA), which has been shown to inhibit mt1 melatonin membrane receptor expression, the neurohormone failed to counteract the effect of PGE(2). Therefore, we postulate, for the first time, a physiological role of the mt1 melatonin membrane receptor in the human immune system.