[Serotonin modulates HIV replication in primary culture of human macrophages: involvement of 5-HT(1A) sub-type receptors].
The neurotransmitter 5-hydroxytryptamine (5-HT), commonly known as serotonin, is released at peripheral sites from activated platelets. At inflammatory sites, macrophages and lymphocytes could be exposed to 5-HT concentrations up to 100 microM. Moreover, 5-HT could modulate cytokine secretion by monocytes/macrophages and immune functions through the uptake of 5-HT at these inflammatory sites from T cells and dendritic cells. HIV infection is also under the control of inflammatory processes (including T cell proliferation and cytokines secretion). On this basis, we studied explored herein the effects of 5-HT on HIV-1/Ba-L (macrophage-tropic virus) replication in primary cultures of human macrophages. This pharmacological study with isotype-selective receptor agonists and antagonist allowed us to show that the 100 microM 5-HT concentration via 5-HT(1A) subtype receptors could decrease HIV replication. This observation was associated with an increase of MIP-1alpha secretion such as an increase of MIP-1alpha mRNA production and with a decrease of HIV-coreceptor CCR5 cell surface expression. Our results point out for the first time the inhibitory effects of 5-HT on HIV replication in primary culture of human macrophages via activation of 5-HT(1A) subtype receptors.
Manéglier
B
B
Pharmacologie, Université Versailles Saint-Quentin, UFR Médicale Paris-Ile-de-France-Ouest, Saint-Quentin-en-Yvelines, France. bmaneglier@ch-versailles.fr
Spreux-Varoquaux
O
O
Guillemin
G-J
GJ
Rogez-Kreuz
C
C
Dormont
D
D
Advenier
C
C
Clayette
P
P
D000998:Antiviral Agents / Q000627:therapeutic use; D006678:HIV / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000821:virology*; D009000:Monocytes / Q000821:virology; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*; D014777:Virus Diseases / Q000175:diagnosis / Q000188:drug therapy; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin