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

C. W. Tsao, Y. S. Lin, J. T. Cheng, C. F. Lin, H. T. Wu, S. R. Wu, W. H. Tsai

Research output: Contribution to journalArticle

37 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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