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

¹ Department of Nursing, Chung Hwa University of Medical Technology, Tainan County, Taiwan
² Department of Microbiology and Immunology, National Cheng Kung University Medical College, Tainan, Taiwan
³ Department of Pharmacology, National Cheng Kung University Medical College, Tainan, Taiwan
⁴ Institute of Clinical Medicine, National Cheng Kung University Medical College, Tainan, Taiwan
⁵ Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan, Taiwan

^* To whom correspondence should be addressed.

	Abstract

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

First published on February 28, 2008, doi:10.1177/0269881107082951

Journal of Psychopharmacology 2008;22:753.

A more recent version of this article appeared on September 1, 2008
This version was published on April 18, 2008


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