Tsao C-W, Lin Y-S, Cheng J-T, Lin C-F, Wu H-T, Wu S-R, Tsai W-H
Department of Nursing, Chung Hwa University of Medical Technology, Tainan County, Taiwan.
J Psychopharmacol. 2008 Sep;22(7):753-60. doi: 10.1177/0269881107082951. Epub 2008 Feb 28.
Interferon (IFN)-alpha upregulates serotonin (5-HT) uptake and serotonin transporter (5-HTT) messenger ribonucleic acid (mRNA) expression in immune cells, which implies the mechanism underlying IFN-alpha-induced depression. However, the signal transduction of this effect remains unclear. We investigated whether the effects of IFN-alpha on the functions of 5-HTT were related to mitogen-activated protein kinase (MAPK). By performing Western blotting, real-time reverse transcriptase-polymerase chain reaction and [3H]5-HT labelling, we examined MAPK phosphorylation, 5-HTT mRNA expression and 5-HT uptake in Jurkat T cells. The cells had been cultured for different time periods (1) with IFN-alpha alone and (2) preincubated with either MAPK inhibitors or with the selective serotonin reuptake inhibitor, fluoxetine, and subsequently cultured along with IFN-alpha. The levels of MAPK phosphorylation, 5-HTT mRNA expression and 5-HT uptake all increased in the IFN-alpha-treated cells but were blocked in those that were pretreated with MAPK inhibitors and fluoxetine. These results appear to clarify the association of depression with IFN-alpha-induced 5-HT uptake that reduces the 5-HT levels and IFN-alpha-regulated transcription of 5-HTT; further, the results suggest the involvement of MAPK in this process.
干扰素（IFN）-α可上调免疫细胞中5-羟色胺（5-HT）摄取及5-羟色胺转运体（5-HTT）信使核糖核酸（mRNA）表达，这提示了IFN-α诱导抑郁的潜在机制。然而，这种效应的信号转导仍不清楚。我们研究了IFN-α对5-HTT功能的影响是否与丝裂原活化蛋白激酶（MAPK）有关。通过蛋白质免疫印迹法、实时逆转录-聚合酶链反应及[3H]5-HT标记，我们检测了Jurkat T细胞中MAPK磷酸化、5-HTT mRNA表达及5-HT摄取情况。细胞在不同时间段进行培养：（1）单独用IFN-α培养；（2）先用MAPK抑制剂或选择性5-羟色胺再摄取抑制剂氟西汀预孵育，随后与IFN-α一起培养。在经IFN-α处理的细胞中，MAPK磷酸化、5-HTT mRNA表达及5-HT摄取水平均升高，但在用MAPK抑制剂和氟西汀预处理的细胞中则受到抑制。这些结果似乎阐明了抑郁与IFN-α诱导的5-HT摄取减少5-HT水平及IFN-α调节5-HTT转录之间的关联；此外，结果提示MAPK参与了这一过程。
