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

36 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 - Sep 2008
Externally publishedYes

Fingerprint

Serotonin Plasma Membrane Transport Proteins
Jurkat Cells
Mitogen-Activated Protein Kinases
Interferons
Serotonin
T-Lymphocytes
Fluoxetine
RNA
Protein Kinase Inhibitors
Phosphorylation
Serotonin Uptake Inhibitors
Reverse Transcriptase Polymerase Chain Reaction
Real-Time Polymerase Chain Reaction
Signal Transduction
Up-Regulation
Western Blotting

Keywords

  • Depression
  • Interferon
  • Mitogen-activated protein kinase
  • Serotonin transporter

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Neuroscience(all)

Cite this

Interferon-α-induced serotonin uptake in Jurkat T cells via mitogen-activated protein kinase and transcriptional regulation of the serotonin transporter. / Tsao, C. W.; Lin, Y. S.; Cheng, J. T.; Lin, C. F.; Wu, H. T.; Wu, S. R.; Tsai, W. H.

In: Journal of Psychopharmacology, Vol. 22, No. 7, 09.2008, p. 753-760.

Research output: Contribution to journalArticle

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