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 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. 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 microM) was also able to induce overexpression of MIP-1alpha mRNA leading to an increase of MIP-1alpha secretion by human macrophages. CONCLUSIONS AND IMPLICATIONS: 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.
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 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. 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 microM) was also able to induce overexpression of MIP-1alpha mRNA leading to an increase of MIP-1alpha secretion by human macrophages. CONCLUSIONS AND IMPLICATIONS: 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.
Authors: Timothy N C Wells; Christine A Power; Jeffrey P Shaw; Amanda E I Proudfoot Journal: Trends Pharmacol Sci Date: 2005-11-28 Impact factor: 14.819
Authors: M R Capobianchi; I Abbate; G Antonelli; O Turriziani; A Dolei; F Dianzani Journal: AIDS Res Hum Retroviruses Date: 1998-02-10 Impact factor: 2.205
Authors: M Freire-Garabal; M J Núñez; J Balboa; P López-Delgado; R Gallego; T García-Caballero; M D Fernández-Roel; J Brenlla; M Rey-Méndez Journal: Br J Pharmacol Date: 2003-05 Impact factor: 8.739
Authors: Dwight L Evans; Kevin G Lynch; Tami Benton; Benoit Dubé; David R Gettes; Nancy B Tustin; Jian Ping Lai; David Metzger; Steven D Douglas Journal: Biol Psychiatry Date: 2007-10-22 Impact factor: 13.382
Authors: Marco Idzko; Elisabeth Panther; Christian Stratz; Tobias Müller; Hannes Bayer; Gernot Zissel; Thorsten Dürk; Stephan Sorichter; Francesco Di Virgilio; Michael Geissler; Bernd Fiebich; Yared Herouy; Peter Elsner; Johannes Norgauer; Davide Ferrari Journal: J Immunol Date: 2004-05-15 Impact factor: 5.422
Authors: Ellen M Bouma; Denise P I van de Pol; Ilson D Sanders; Izabela A Rodenhuis-Zybert; Jolanda M Smit Journal: J Virol Date: 2020-06-16 Impact factor: 5.103
Authors: Jeffrey M Greeson; David R Gettes; Sergei Spitsin; Benoit Dubé; Tami D Benton; Kevin G Lynch; Steven D Douglas; Dwight L Evans Journal: Biol Psychiatry Date: 2015-11-10 Impact factor: 13.382
Authors: Thangavel Samikkannu; Kurapati V K Rao; Nimisha Gandhi; Shailendra K Saxena; Madhavan P N Nair Journal: J Neurovirol Date: 2010-07 Impact factor: 2.643
Authors: Tami Benton; Kevin Lynch; Benoit Dubé; David R Gettes; Nancy B Tustin; Jian Ping Lai; David S Metzger; Joshua Blume; Steven D Douglas; Dwight L Evans Journal: Psychosom Med Date: 2010-10-14 Impact factor: 4.312
Authors: Kelly A Meulendyke; Suzanne E Queen; Elizabeth L Engle; Erin N Shirk; Jiayang Liu; Joseph P Steiner; Avindra Nath; Patrick M Tarwater; David R Graham; Joseph L Mankowski; M Christine Zink Journal: J Neurovirol Date: 2014-09-17 Impact factor: 2.643
Authors: Benjamin B Gelman; Joshua G Lisinicchia; Tianshen Chen; Kenneth M Johnson; Kristofer Jennings; Daniel H Freeman; Vicki M Soukup Journal: J Neuroimmune Pharmacol Date: 2012-03-06 Impact factor: 4.147
Authors: Rodrigo Arreola; Enrique Becerril-Villanueva; Carlos Cruz-Fuentes; Marco Antonio Velasco-Velázquez; María Eugenia Garcés-Alvarez; Gabriela Hurtado-Alvarado; Saray Quintero-Fabian; Lenin Pavón Journal: J Immunol Res Date: 2015-04-19 Impact factor: 4.818