Interferon-α-induced modulation of glucocorticoid and serotonin receptors as a mechanism of depression

Wei Cai, Vladimir I. Khaoustov, Qing Xie, Tianhong Pan, Weidong Le, Boris Yoffe

Research output: Contribution to journalArticle

76 Scopus citations

Abstract

Background/Aims: The mechanism of interferon (IFN)-α-induced depression remains poorly understood. Recently, modulation of glucocorticoid receptor (GR) and serotonin receptor 1A (5-HTR1A) were implicated in mechanism(s) leading to depression. To gain insight into this mechanism, we assessed the effect of IFN-α on the modulation of GR and 5-HTR1A expression. Methods: Hepatoblastoma, myelocyte-derived and T cell leukemia-derived cell lines were treated with titrated doses of IFN-α for different incubation times and analyzed by Western blot, RT-PCR, and microarrays. Dose- and time-dependent decreases of proteins and mRNA levels of GR and 5-HTR1A were observed. Results: The expression of GR and 5-HTR1A in cells treated for 6 days decreased by 74 and 72%, respectively. Recovery was observed following IFN-α withdrawal. Co-incubation with tricyclic antidepressants (desipramine) or serotonin reuptake inhibitors (fluoxetine) attenuated the effect of IFN-α on GR or 5-HTR1A. GR and 5-HTR1A were unaffected by treatment with either IFN-γ or tauroursodeoxycholic acid (TUDCA). However, the effect of IFN-α on GR was abolished when used in combination with TUDCA. Conclusions: In conclusion, IFN-α downregulated GR and 5-HTR1A levels in cell lines. These levels of GR and 5-HTR1A, following IFN-α-induced downregulation, recovered after withdrawal of IFN-α or addition of desipramine or fluoxetine. These data provide insights regarding pathogenesis of IFN-α-induced depression.

Original languageEnglish (US)
Pages (from-to)880-887
Number of pages8
JournalJournal of Hepatology
Volume42
Issue number6
DOIs
StatePublished - Jun 2005

Keywords

  • Depression
  • Glucocorticoid receptor
  • HCV
  • Interferon
  • Serotonin receptor

ASJC Scopus subject areas

  • Gastroenterology

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