Serotonin decreases HIV‐1 replication in primary cultures of human macrophages through 5‐HT_1A receptors

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 mM) 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-1a (MIP-1a), was quantified by ELISA in cell culture supernatants and MIP-1a 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 mM) was also able to induce overexpression of MIP-1a mRNA leading to an increase of MIP-1a secretion by human macrophages. Conclusions and implications:The effects of 5-HT on HIV infection could be a consequence of the increase in MIP-1a 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.

Plasma tryptophan, kynurenine and 3-hydroxykynurenine measurement using automated on-line solid-phase extraction HPLC–tandem mass spectrometry

“…The expression of IDO is induced during inflammation and infectious diseases by proinflammatory stimuli and T-helper-cell (T H -cell) cytokines such as interferon-␥. Furthermore IDO appears to play a role in immunoregulation and communication between the immune and nervous systems [1,2,[4][5][6] and is suggested to mediate the tumor immune escape [7]. Another kynurenine pathway metabolite, 3-hydroxykynurenine, causes neuronal damage and cell death mediated by free radicals in a neuronal hybrid cell line and the rat striatum [2,8].…”

“…Tryptophan metabolism plays a key role in several (patho)physiological processes, such as the endocrine manifestations of neuroendocrine tumors, i.e., carcinoid tumors with excessive serotonin production [9], mood disorders such as depression with decreased serotonin production [10], inflammation, immune-activation, transplantation [1,2,[4][5][6] and pregnancy [10]. The metabolic fate of tryptophan ( Fig.…”

Optimization of Zn2+-containing mobile phase for simultaneous determination of kynurenine, kynurenic acid and tryptophan in human plasma by high performance liquid chromatography

“…Normally ultraviolet (UV) detection was employed to determine KYN [6][7][8][9][10][11] and fluorescence detection was used to measure KYNA and TRP [5][6][7][8][9][10][12][13][14][15][16][17]. Besides, some other techniques were also reported to determine TRP and kynurenines, e.g., measuring KYN and TRP by coulometric detection [18]; KYNA by capillary electrophoresis with laser-induced fluorescence detection [19]; and TRP and related compounds by high performance liquid chromatography-mass spectrometry (HPLC-MS) [20][21][22].…”

Serotonin activates murine alveolar macrophages through 5-HT2Creceptors

“…Serotonin receptors build up a large family including ionotropic cation channels (5-HT 3 ) and six types of metabotropic G protein-coupled receptors (20). Various subtypes of metabotropic 5-HT receptors have been identified on B cells, T cells, dendritic cells, peripheral blood mononuclear leukocytes, and macrophages (6,10,16,21,30,35,36). In inflammatory states in general, 5-HT regulates cell growth and division, cytokine synthesis, and chemotaxis (1,24,37,51).…”