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


METHODS
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.


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 microM) was also able to induce overexpression of MIP-1alpha mRNA leading to an increase of MIP-1alpha secretion by human macrophages.


CONCLUSIONS
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.
Manéglier
B
B
UPRES EA 220, UFR Médicale Paris-Ile de France-Ouest, Université Versailles St-Quentin, Saint-Quentin en Yvelines, France. bmaneglier@ch-versailles.fr
Guillemin
G J
GJ
Clayette
P
P
Rogez-Kreuz
C
C
Brew
B J
BJ
Dormont
D
D
Advenier
C
C
Therond
P
P
Spreux-Varoquaux
O
O
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D015704:CD4 Antigens / Q000096:biosynthesis; D002478:Cells, Cultured; D004279:DNA, Viral / Q000096:biosynthesis; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008264:Macrophages / Q000821:virology*; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects*; D019713:Receptors, CCR5 / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D015704:CD4 Antigens; D004279:DNA, Viral; D010879:Piperazines; D011725:Pyridines; D012333:RNA, Messenger; D019713:Receptors, CCR5; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D048051:p38 Mitogen-Activated Protein Kinases