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

C. W. Tsao, Yee-Shin Lin, J. T. Cheng, C. F. Lin, H. T. Wu, S. R. Wu, W. H. Tsai

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)

Abstract

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

Original languageEnglish
Pages (from-to)753-760
Number of pages8
JournalJournal of Psychopharmacology
Volume22
Issue number7
DOIs
Publication statusPublished - 2008 Sep 1

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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