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Serotonin decreases HIV-1 replication in primary cultures of human macrophages through 5-HT1A receptors

Identifieur interne : 000355 ( Ncbi/Curation ); précédent : 000354; suivant : 000356

Serotonin decreases HIV-1 replication in primary cultures of human macrophages through 5-HT1A receptors

Auteurs : B. Manéglier [France] ; G J Guillemin [Australie] ; P. Clayette [France] ; C. Rogez-Kreuz [France] ; B J Brew [Australie] ; D. Dormont [France] ; C. Advenier [France] ; P. Therond [France] ; O. Spreux-Varoquaux [France]

Source :

RBID : PMC:2438982

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-HT1A and 5-HT2 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-HT1A 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-HT1A receptors.


Url:
DOI: 10.1038/bjp.2008.80
PubMed: 18332855
PubMed Central: 2438982

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PMC:2438982

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Fontenay-aux-Roses,
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Fontenay-aux-Roses,
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Fontenay-aux-Roses,
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Fontenay-aux-Roses,
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Saint-Quentin en Yvelines,
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Le Chesnay,
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Saint-Quentin en Yvelines,
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Le Chesnay,
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<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<front>
<div type="abstract" xml:lang="en">
<p>
<bold>Background and purpose:</bold>
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
<italic>in vitro</italic>
.</p>
<p>
<bold>Experimental approach:</bold>
Human macrophages cultured in serum-free medium were treated over 7 days with 5-HT at three concentrations (0.01, 1 and 100 μ
<sc>M</sc>
) with or without agonists and antagonists of 5-HT
<sub>1A</sub>
and 5-HT
<sub>2</sub>
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.</p>
<p>
<bold>Key results:</bold>
<italic>In vitro</italic>
, 5-HT downregulated the membranous expression of CCR5 and led to a decrease of HIV-1 infection, probably through its action on 5-HT
<sub>1A</sub>
receptors. 5-HT (100 μ
<sc>M</sc>
) was also able to induce overexpression of MIP-1α mRNA leading to an increase of MIP-1α secretion by human macrophages.</p>
<p>
<bold>Conclusions and implications:</bold>
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
<sub>1A</sub>
receptors.</p>
</div>
</front>
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