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Interferon--induced serotonin uptake in Jurkat T cells via mitogen-activated protein kinase and transcriptional regulation of the serotonin transporter

Department of Nursing, Chung Hwa University of Medical Technology, Tainan County, Taiwan, tcwhmy{at}ms58.hinet.net

Y-S. Lin

Department of Microbiology and Immunology, National Cheng Kung University Medical College, Tainan, Taiwan

J-T. Cheng

Department of Pharmacology, National Cheng Kung University Medical College, Tainan, Taiwan

C-F. Lin

Institute of Clinical Medicine, National Cheng Kung University Medical College, Tainan, Taiwan

H-T. Wu

Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan, Taiwan

S-R. Wu

Department of Microbiology and Immunology, National Cheng Kung University Medical College, Tainan, Taiwan

W-H. Tsai

Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan, Taiwan

Interferon (IFN)- upregulates serotonin (5-HT) uptake and serotonin transporter (5-HTT) messenger ribonucleic acid (mRNA) expression in immune cells, which implies the mechanism underlying IFN--induced depression. However, the signal transduction of this effect remains unclear. We investigated whether the effects of IFN- 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- alone and (2) preincubated with either MAPK inhibitors or with the selective serotonin reuptake inhibitor, fluoxetine, and subsequently cultured along with IFN-. The levels of MAPK phosphorylation, 5-HTT mRNA expression and 5-HT uptake all increased in the IFN--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--induced 5-HT uptake that reduces the 5-HT levels and IFN--regulated transcription of 5-HTT; further, the results suggest the involvement of MAPK in this process.

Key Words: depression • interferon • mitogen-activated protein kinase • serotonin transporter

This version was published on September 1, 2008

Journal of Psychopharmacology, Vol. 22, No. 7, 753-760 (2008)
DOI: 10.1177/0269881107082951


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