Paroxetine differentially modulates LPS-induced TNFα and IL-6 production in mouse macrophages.
Paroxetine differentially modulates LPS-induced TNFα and IL-6 production in mouse macrophages.
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DOI：
10.1016/j.intimp.2015.02.029
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发表时间：
2015-04
影响因子：
5.6
通讯作者：
Parameswaran N
中科院分区：
文献类型：
--
作者：
Durairaj H;Steury MD;Parameswaran N
帕罗西汀是一种选择性5-羟色胺再摄取抑制剂（SSRI），临床上用于治疗人类患者的抑郁症。由于最近有报道称血清素在调节炎症中的作用以及炎症和抑郁症之间的联系，我们试图直接测试帕罗西汀对巨噬细胞对炎症刺激的反应的影响。脂多糖（LPS）处理小鼠巨噬细胞显著增加TNFα和IL-6的产生。然而，帕罗西汀治疗巨噬细胞，显着抑制LPS诱导的IL-6的产生。相反，帕罗西汀增强LPS诱导的巨噬细胞TNFα的产生。帕罗西汀的这些作用被另一种SSRI药物氟西汀模仿。为了确定帕罗西汀的作用是否通过调节5-HT系统介导，我们在LPS和/或帕罗西汀存在下用5-HT或5-HT受体拮抗剂（LY 215840）处理巨噬细胞。5-HT处理本身不影响LPS诱导的细胞因子产生。然而，LY 215840逆转帕罗西汀对LPS诱导的TNFα产生的作用，但不逆转IL-6。为了了解信号转导机制，我们检测了帕罗西汀对MAPK和NFκB通路的影响。虽然帕罗西汀抑制LPS诱导的IκBα磷酸化，但MAPK途径基本不受影响。总之，这些数据表明帕罗西汀对巨噬细胞中IL-6和TNFα的产生具有关键但不同的作用，并且可能通过不同的机制调节这些细胞因子。
Paroxetine is a selective serotonin reuptake inhibitor (SSRI) that is clinically used for the treatment of depression in human patients. Because of recent reports on the role of serotonin in modulating inflammation and the link between inflammation and depression, we sought to test the effect of paroxetine directly on macrophage response to an inflammatory stimulus. Lipopolysaccharide (LPS) treatment of mouse macrophages significantly enhanced TNFα and IL-6 production. Paroxetine treatment of macrophages however, significantly inhibited LPS-induced IL-6 production. In contrast, paroxetine enhanced LPS-induced TNFα production in macrophages. These effects of paroxetine were mimicked by fluoxetine, another SSRI. To determine if the effects of paroxetine are mediated via modulation of the 5-HT system, we treated macrophages with 5-HT or 5-HT receptor antagonist (LY215840) in the presence of LPS and/or paroxetine. 5-HT treatment by itself did not affect LPS-induced cytokine production. LY215840 however, reversed paroxetine's effect on LPS-induced TNFα production but not IL-6. To understand the signaling mechanisms, we examined paroxetine's effect on MAPK and NFκB pathways. While paroxetine inhibited LPS-induced IκBα phosphorylation, MAPK pathways were mostly unaffected. Together these data demonstrate that paroxetine has critical but differential effects on IL-6 and TNFα production in macrophages and that it likely regulates these cytokines via distinct mechanisms.
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影响因子：
5.6
作者：
Patial, Sonika;Saini, Yogesh;Parvataneni, Sitaram;Appledorn, Daniel M.;Dorn, Gerald W., II;Lapres, John J.;Amalfitano, Andrea;Senagore, Patricia;Parameswaran, Narayanan
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影响因子：
10.6
作者：
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通讯作者：
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作者：
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