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

71Citations
Citations of this article
52Readers
Mendeley users who have this article in their library.

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. © 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Cite

CITATION STYLE

APA

Cai, W., Khaoustov, V. I., Xie, Q., Pan, T., Le, W., & Yoffe, B. (2005). Interferon-α-induced modulation of glucocorticoid and serotonin receptors as a mechanism of depression. Journal of Hepatology, 42(6), 880–887. https://doi.org/10.1016/j.jhep.2005.01.024

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free