Serotonin transporter mRNA expression is decreased by lamivudine and ribavirin and increased by interferon in immune cells.
Clinical reports document that depression as a side effect is more prevalent in hepatic patients given interferon (IFN)-alpha therapy than in those given lamivudine. The mechanisms, however, are poorly understood. Serotonin transporter (5-HTT), via uptake of serotonin (5-HT) into presynaptic serotoninergic neurons, is an initial action site for antidepressants. Real-time polymerase chain reaction (PCR) was used to quantify 5-HTT mRNA expression in immune cells in order to evaluate whether 5-HTT acted as an indicator of depression. Results showed that the 5-HTT mRNA expression was much higher in T-cell and B-cell lines than that in a monocytic cell line. Treatment with either lamivudine or ribavirin reduced the 5-HTT mRNA expression, protein level and 5-HT uptake in T-cell line. Treatment with IFN-alpha, however, increased those levels in the same group. A similar effect was observed in peripheral blood mononuclear cells (PBMC). Mimicking clinical use by treating PBMC with a combination of IFN-alpha and ribavirin increased the 5-HTT mRNA expression level. Our study indicates that these therapeutic drugs regulate 5-HTT expression, which implies that 5-HTT might be a trait marker in IFN-alpha-induced depression after hepatic therapy.
Department of Nursing, Chung Hwa College of Medical Technology, Tainan County, Taiwan. tcwhmy@ms58.hinet.net
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D000998:Antiviral Agents / Q000494:pharmacology*; D015153:Blotting, Western; D003863:Depression / Q000139:chemically induced / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006505:Hepatitis / Q000188:drug therapy; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D019169:Jurkat Cells; D019259:Lamivudine / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D012367:RNA, Viral / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012254:Ribavirin / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000096:biosynthesis / Q000235:genetics*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D020298:U937 Cells
D000998:Antiviral Agents; D016898:Interferon-alpha; D012333:RNA, Messenger; D012367:RNA, Viral; D050486:Serotonin Plasma Membrane Transport Proteins; D019259:Lamivudine; D012701:Serotonin; D012254:Ribavirin