Interferon-alpha-induced serotonin uptake in Jurkat T cells via mitogen-activated protein kinase and transcriptional regulation of the serotonin transporter.
Interferon (IFN)-alpha upregulates serotonin (5-HT) uptake and serotonin transporter (5-HTT) messenger ribonucleic acid (mRNA) expression in immune cells, which implies the mechanism underlying IFN-alpha-induced depression. However, the signal transduction of this effect remains unclear. We investigated whether the effects of IFN-alpha 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-alpha alone and (2) preincubated with either MAPK inhibitors or with the selective serotonin reuptake inhibitor, fluoxetine, and subsequently cultured along with IFN-alpha. The levels of MAPK phosphorylation, 5-HTT mRNA expression and 5-HT uptake all increased in the IFN-alpha-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-alpha-induced 5-HT uptake that reduces the 5-HT levels and IFN-alpha-regulated transcription of 5-HTT; further, the results suggest the involvement of MAPK in this process.
Tsao
C-W
CW
Department of Nursing, Chung Hwa University of Medical Technology, Tainan County, Taiwan. tcwhmy@ms58.hinet.net
Lin
Y-S
YS
Cheng
J-T
JT
Lin
C-F
CF
Wu
H-T
HT
Wu
S-R
SR
Tsai
W-H
WH
D000998:Antiviral Agents / Q000494:pharmacology*; D015153:Blotting, Western; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D019169:Jurkat Cells; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000096:biosynthesis* / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000998:Antiviral Agents; D016898:Interferon-alpha; D012333:RNA, Messenger; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases