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

British Journal of Pharmacology

metabolism, p38 Mitogen-Activated Protein Kinases, drug effects, Virus Replication, pharmacology, Serotonin Receptor Agonists, Serotonin Antagonists, Serotonin 5-HT1 Receptor Antagonists, Serotonin 5-HT1 Receptor Agonists, Serotonin, Receptors, CCR5, Receptor, Serotonin, 5-HT1A, genetics, biosynthesis, RNA, Messenger, Pyridines, Piperazines, virology, Macrophages, Humans, HIV-1, DNA, Viral, Cells, Cultured, Antigens, CD4, 8-Hydroxy-2-(di-n-propylamino)tetralin

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      Abstract

      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. Human macrophages cultured in serum-free medium were treated over 7 days with 5-HT at three concentrations (0.01, 1 and 100 microM) 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-1alpha (MIP-1alpha), was quantified by ELISA in cell culture supernatants and MIP-1alpha mRNA expression was assessed by reverse transcriptase-PCR. 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 microM) was also able to induce overexpression of MIP-1alpha mRNA leading to an increase of MIP-1alpha secretion by human macrophages. The effects of 5-HT on HIV infection could be a consequence of the increase in MIP-1alpha 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.

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      Journal
      10.1038/bjp.2008.80
      2438982
      18332855

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