Serotonin decreases HIV-1 replication in primary cultures of human macrophages through 5-HT 1A receptors

B. Manéglier*, G. J. Guillemin, P. Clayette, C. Rogez-Kreuz, B. J. Brew, D. Dormont, C. Advenier, P. Therond, O. Spreux-Varoquaux

*Corresponding author for this work

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Abstract

Background and purpose: 5-HT (serotonin) is known to be involved in neuroinflammation and immunoregulation. The human immunodeficiency virus (HIV) targets cells such as monocytes/macrophages, which colocalize with 5-HT-releasing cell types, mostly platelets. In this study, we investigated the effects of 5-HT on HIV-1-infected macrophages in vitro. Experimental approach: Human macrophages cultured in serum-free medium were treated over 7 days with 5-HT at three concentrations (0.01, 1 and 100 μM) with or without agonists and antagonists of 5-HT 1A and 5-HT 2 receptors. After 7 days of treatment, macrophages were infected with HIV-1/Ba-L and virus replication was monitored over 16 days and expression of proviral HIV DNA was investigated by PCR after 24 h of infection. Cell surface expression of HIV-1/Ba-L receptor (CD4) and coreceptor (CCR5) was investigated by flow cytometry. The CCR5 ligand, macrophage inflammatory protein-1α (MIP-1α), was quantified by ELISA in cell culture supernatants and MIP-1α mRNA expression was assessed by reverse transcriptase-PCR. Key results: In vitro, 5-HT downregulated the membranous expression of CCR5 and led to a decrease of HIV-1 infection, probably through its action on 5-HT 1A receptors. 5-HT (100 μM) was also able to induce overexpression of MIP-1α mRNA leading to an increase of MIP-1α secretion by human macrophages. Conclusions and implications: The effects of 5-HT on HIV infection could be a consequence of the increase in MIP-1α concentrations and/or CCR5 receptor downregulation. These results suggest that 5-HT can inhibit the replication of HIV-1 in primary culture of human macrophages through its action on 5-HT 1A receptors.

Original languageEnglish
Pages (from-to)174-182
Number of pages9
JournalBritish Journal of Pharmacology
Volume154
Issue number1
DOIs
Publication statusPublished - May 2008
Externally publishedYes

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    Manéglier, B., Guillemin, G. J., Clayette, P., Rogez-Kreuz, C., Brew, B. J., Dormont, D., ... Spreux-Varoquaux, O. (2008). Serotonin decreases HIV-1 replication in primary cultures of human macrophages through 5-HT 1A receptors. British Journal of Pharmacology, 154(1), 174-182. https://doi.org/10.1038/bjp.2008.80