Fluoxetine suppresses calcium signaling in human T lymphocytes through depletion of intracellular calcium stores
Fluoxetine suppresses calcium signaling in human T lymphocytes through depletion of intracellular calcium stores
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DOI：
10.1016/j.ceca.2015.06.003
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发表时间：
2015-09-01
期刊：
影响因子：
4
通讯作者：
Deforce, D.
中科院分区：
文献类型：
--
作者：
Gobin, V.;De Bock, M.;Deforce, D.
选择性血清素再摄取抑制剂，例如氟西汀，最近被证明具有抗炎和免疫抑制作用。尽管对 T 淋巴细胞的细胞因子分泌、增殖和活力的影响已得到广泛表征，但人们对这些影响背后的机制知之甚少。众所周知，Ca2+信号传导是T细胞受体激活后信号转导途径中的重要步骤。因此，我们研究了氟西汀是否干扰 Jurkat T 淋巴细胞中的 Ca2+ 信号传导。发现氟西汀可抑制 T 细胞受体激活时的 Ca2+ 信号传导。此外，发现氟西汀会耗尽细胞内的 Ca2+ 储备，从而在 IP3 和兰尼碱受体激活时留下较少的可释放的 Ca2+。氟西汀的 Ca2+ 修饰作用与其阻断血清素转运蛋白的能力无关，因为即使大量过量的 5HT 也不会消除这种作用。总之，这些数据表明氟西汀减少了 Jurkat T 淋巴细胞中 IP3 和兰尼定受体介导的 Ca2+ 释放，这种作用可能是观察到的免疫抑制的基础。 (C) 2015 年作者。由 Elsevier Ltd 出版。这是一篇遵循 CC BY-NC-ND 许可证 (http://creativecommons.org/licenses/by-nc-nd/4.0/) 的开放获取文章。
Selective serotonin reuptake inhibitors, such as fluoxetine, have recently been shown to exert anti-inflammatory and immunosuppressive effects. Although the effects on cytokine secretion, proliferation and viability of T lymphocytes have been extensively characterized, little is known about the mechanism behind these effects. It is well known that Ca2+ signaling is an important step in the signaling transduction pathway following T cell receptor activation. Therefore, we investigated if fluoxetine interferes with Ca2+ signaling in Jurkat T lymphocytes. Fluoxetine was found to suppress Ca2+ signaling in response to T cell receptor activation. Moreover, fluoxetine was found to deplete intracellular Ca2+ stores, thereby leaving less Ca2+ available for release upon IP3- and ryanodine-receptor activation. The Ca2+-modifying effects of fluoxetine are not related to its capability to block the serotonin transporter, as even a large excess of 5HT did not abolish the effects. In conclusion, these data show that fluoxetine decreases IP3- and ryanodine-receptor mediated Ca2+ release in Jurkat T lymphocytes, an effect likely to be at the basis of the observed immunosuppression. (C) 2015 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).