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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 Psychology, London Metropolitan University, Old Castle Street, London E1 7NT, UK.
² Department of Psychology, University of Greenwich, Avery Hill Road, Eltham, London SE9 2UG, UK.

^* 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


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