Serotonin Upregulates Mitogen-Stimulated B Lymphocyte Proliferation through 5-HT1AReceptors

Iken, Khadija; Chheng, Susana; Fargin, Annick; Goulet, Anne-Christine; Kouassi, Édouard

doi:10.1006/cimm.1995.1092

Cited by 132 publications

(108 citation statements)

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“…In functional studies using selective agonists and antagonists, it has been shown that the 5-HT 1A receptor is implicated in the regulation of T cell responses including human T-cell proliferation (13)(14)(15)(16), production of Th1 cytokines such as interleukin-2 and interferon-␥ both in mice (17) and in human (15,16), and contact sensitivity reactions in mice (17). We have shown previously that mitogen-stimulated B lymphocyte proliferation in rodents is up-regulated by 5-HT via specific interaction with the 5-HT 1A receptor (18). Thus, immune and inflammatory responses may be regulated in part through 5-HT 1A receptor expression in B and T lymphocytes.…”

Section: Serotonin (5-ht)mentioning

confidence: 93%

“…The previous studies cited above using essentially functional and radioligand binding criteria suggest that 5-HT 1A receptor expression is increased following mitogenic stimulation of both murine B cells (18) and human T cells (13), but little is known about the molecular mechanisms underlying this effect. Nuclear factor-B (NF-B) is a ubiquitous and inducible transcription factor involved in many immune and inflammatory responses, including activation and proliferation of B and T lymphocytes stimulated by mitogens such as LPS, PHA, and PMA (19 -21).…”

Section: Serotonin (5-ht)mentioning

confidence: 99%

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Transcriptional Mechanisms for Induction of 5-HT1AReceptor mRNA and Protein in Activated B and T Lymphocytes

Abdouh

Storring

Riad

et al. 2001

Journal of Biological Chemistry

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Serotonin (5-HT)1 is a neuroimmunomodulator that is widely distributed in brain and peripheral tissues, and which is released by activated platelets during the course of tissue inflammation (1). 5-HT is also accumulated by and released from noradrenergic nerve terminals that are in close contact with lymphocytes in lymphoid organs (2-4). Rodent mast cells are another important source which release their stored 5-HT following exposure to antigen and IgE-sensitizing Ab, or to neuropeptides such as somatostatin, substance P, calcitonin generelated peptide, and vasoactive intestinal peptide, the latter being released from peripheral nerves (5).Among the numerous 5-HT receptors, 5-HT 1A belongs to G-protein-coupled receptor superfamily and is also widely distributed in brain and immune tissues (6, 7). The 5-HT 1A gene has been cloned previously in human (8, 9), rat (10), and mouse (11), manifesting very high nucleotide and amino acid sequence homology in their respective putative transmembrane regions. 5-HT 1A mRNA has been detected in various human tissues including lymph nodes, spleen, and thymus (8), as well as in human peripheral blood mononuclear cells (12) and activated T lymphocytes (13). In functional studies using selective agonists and antagonists, it has been shown that the 5-HT 1A receptor is implicated in the regulation of T cell responses including human T-cell proliferation (13-16), production of Th1 cytokines such as interleukin-2 and interferon-␥ both in mice (17) and in human (15,16), and contact sensitivity reactions in mice (17). We have shown previously that mitogen-stimulated B lymphocyte proliferation in rodents is up-regulated by 5-HT via specific interaction with the 5-HT 1A receptor (18). Thus, immune and inflammatory responses may be regulated in part through 5-HT 1A receptor expression in B and T lymphocytes.A recent review of the role of 5-HT in the immune system and in neuroimmune interactions has underscored the necessity of characterizing the distribution of the various 5-HT receptors in different immune cell populations, preferably by using molecular biological methods (7). The previous studies cited above using essentially functional and radioligand binding criteria suggest that 5-HT 1A receptor expression is increased following mitogenic stimulation of both murine B cells (18) and human T cells (13), but little is known about the molecular mechanisms underlying this effect. Nuclear factor-B (NF-B) is a ubiquitous and inducible transcription factor involved in many immune and inflammatory responses, including activation and proliferation of B and T lymphocytes stimulated by mitogens such as LPS, PHA,. NF-B is mainly composed of p50 and p65 subunits, which are normally retained in the cytosol of nonstimulated cells by inhibitory molecules, IB. In response to stimuli, IB are rapidly phosphorylated and degraded, allowing translocation of NF-B complexes into the nucleus and activation of NF-B elements (22).In this report, we used RNase protection assay to quantitate the expression of 5-H...

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Section: Serotonin (5-ht)mentioning

confidence: 93%

Section: Serotonin (5-ht)mentioning

confidence: 99%

Transcriptional Mechanisms for Induction of 5-HT1AReceptor mRNA and Protein in Activated B and T Lymphocytes

Abdouh

Storring

Riad

et al. 2001

Journal of Biological Chemistry

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“…5-HT has been found to augment interferon-γ-induced phagocytosis [6] and natural killer cytotoxicity of human CD16 + \non-T-lymphocytes [7]. Recently there has been an upsurge of information indicating that 5-HT can stimulate the immune system via lymphocyte membrane receptors [3,[8][9][10][11]. As far as the multiplicity of serotonergic receptors is concerned [12], it is considered that the 5-HT " class consists of at least five subtypes, namely 5-HT "A, 5-HT "B, 5-HT "D , 5-HT "E and 5-HT "F , which are coupled to Gproteins.…”

Section: Introductionmentioning

confidence: 99%

“…It has been shown that 5-HT up-regulates, in a dose-dependent manner, mitogen-stimulated B-lymphocyte proliferation via 5-HT "A receptors present on these cells [8]. Hence 5-HT and the agonists of 5-HT "A receptors promote the transition of murine Bcells from G !…”

Section: Introductionmentioning

confidence: 99%

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Ionotrophic 5-hydroxytryptamine type 3 receptor activates the protein kinase C-dependent phospholipase D pathway in human T-cells

Khan

Hichami

1999

Biochemical Journal

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The present study was undertaken to investigate the role of the 5-hydroxytryptamine (5-HT) ionotrophic receptor 5-HT3 in the activation of human Jurkat T-cells. 5-HT and 2-methyl-5-HT (2Me-5-HT), an agonist of the 5-HT3 receptor, induced increases in intracellular free Na+ concentrations, [Na+]i, via opening of the ionotrophic receptor in these cells. These two serotonergic (5-hydroxytryptaminergic) agents potentiated phytohaemagglutinin (PHA)-induced T-cell activation. However, they failed to potentiate dioctanoglycerol-plus-ionomycin-stimulated T-cell blastogenesis. Interestingly, an inhibitor of protein kinase C (PKC), GF 109203X, curtailed significantly 5-HT and 2Me-5-HT-potentiated T-cell activation. These results demonstrate that the opening of the 5-HT3 ionotrophic receptor is implicated in T-cell activation via the PKC pathway. Furthermore, 5-HT and 2Me-5-HT stimulated phospholipase D (PLD) activity, as measured by the production of phosphatidylethanol and phosphatidylbutanol at the expense of phosphatidic acid (PA). GF 109203X significantly curtailed the 5-HT- and 2Me-5-HT-induced PLD activity and T-cell activation. The PLD/PA pathway stimulated by these two serotonergic agents resulted in the production of 1,2-diacylglycerol (DAG) mass in Jurkat T-cells. These results altogether suggest that 5-HT and 2Me-5-HT potentiate T-cell activation via increases in [Na+]i and the activation of the PKC-dependent PLD pathway.

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Serotonin signalling in cancer: Emerging mechanisms and therapeutic opportunities

Chen,

Huang,

et al. 2024

Clinical & Translational Med

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BackgroundSerotonin (5‐hydroxytryptamine) is a multifunctional bioamine serving as a neurotransmitter, peripheral hormone and mitogen in the vertebrate system. It has pleiotropic activities in central nervous system and gastrointestinal function via an orchestrated action of serotonergic elements, particularly serotonin receptor‐mediated signalling cascades. The mitogenic properties of serotonin have garnered recognition for years and have been exploited for repurposing serotonergic‐targeted drugs in cancer therapy. However, emerging conflicting findings necessitate a more comprehensive elucidation of serotonin's role in cancer pathogenesis.Main body and conclusionHere, we provide an overview of the biosynthesis, metabolism and action modes of serotonin. We summarise our current knowledge regarding the effects of the peripheral serotonergic system on tumourigenesis, with a specific emphasis on its immunomodulatory activities in human cancers. We also discuss the dual roles of serotonin in tumour pathogenesis and elucidate the potential of serotonergic drugs, some of which display favourable safety profiles and impressive efficacy in clinical trials, as a promising avenue in cancer treatment.Key points Primary synthesis and metabolic routes of peripheral 5‐hydroxytryptamine in the gastrointestinal tract. Advanced research has established a strong association between the serotonergic components and carcinogenic mechanisms. The interplay between serotonergic signalling and the immune system within the tumour microenvironment orchestrates antitumour immune responses. Serotonergic‐targeted drugs offer valuable clinical options for cancer therapy.

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Serotonin Upregulates Mitogen-Stimulated B Lymphocyte Proliferation through 5-HT1AReceptors

Cited by 132 publications

References 0 publications

Transcriptional Mechanisms for Induction of 5-HT1AReceptor mRNA and Protein in Activated B and T Lymphocytes

Transcriptional Mechanisms for Induction of 5-HT1AReceptor mRNA and Protein in Activated B and T Lymphocytes

Ionotrophic 5-hydroxytryptamine type 3 receptor activates the protein kinase C-dependent phospholipase D pathway in human T-cells

Serotonin signalling in cancer: Emerging mechanisms and therapeutic opportunities

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