Prolactin induces calcium influx and release from intracellular pools in human T lymphocytes by activation of tyrosine kinases

Alfonso, Amparo; Botana, Manuel; Vieytes, Mercedes R.; Botana, Luís M.

doi:10.1016/s0898-6568(01)00212-1

Cited by 6 publications

(3 citation statements)

References 23 publications

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“…Peripheral lymphocytes were isolated from human fresh heparinized blood from healthy volunteers as previously described ( 23 ). The blood was diluted in the same proportion with PBS plus EDTA 2 mM previously equilibrated at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Spongionella Secondary Metabolites, Promising Modulators of Immune Response through CD147 Receptor Modulation

et al. 2016

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The modulation of the immune system can have multiple applications such as cancer treatment, and a wide type of processes involving inflammation where the potent chemotactic agent cyclophilin A (Cyp A) is implicated. The Porifera phylum, in which Spongionella is encompassed, is the main producer of marine bioactive compounds. Four secondary metabolites obtained from Spongionella (Gracilin H, A, L, and Tetrahydroaplysulphurin-1) were described to hit Cyp A and to block the release of inflammation mediators. Based on these results, some role of Spongionella compounds on other steps of the signaling pathway mediated by this chemotactic agent can be hypothesized. In the present paper, we studied the effect of these four compounds on the surface membrane CD147 receptor expression, on the extracellular levels of Cyp A and on the ability to migrate of concanavalin (Con A)-activated T lymphocytes. Similar to a well-known immunosuppressive agent cyclosporine A (CsA), Gracilin H, A, L, and tetrahydroaplysulphurin-1 were able to reduce the CD147 membrane expression and to block the release of Cyp A to the medium. Besides, by using Cyp A as chemotactic agent, T cell migration was inhibited when cells were previously incubated with Gracilin A and Gracilin L. These positive results lead us to test the in vivo effect of Gracilin H and L in a mouse ear delayed hypersensitive reaction. Thus, both compounds efficiently reduce the ear swelling as well as the inflammatory cell infiltration. These results provide more evidences for their potential therapeutic application in immune-related diseases of Spongionella compounds.

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Section: Methodsmentioning

confidence: 99%

Spongionella Secondary Metabolites, Promising Modulators of Immune Response through CD147 Receptor Modulation

et al. 2016

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“…Peripheral lymphocytes were isolated from human fresh heparinised blood from healthy volunteers as previously described (Alfonso et al, 2001). The blood was diluted in the same proportion with PBS plus EDTA 2 mM previously equilibrated at room temperature.…”

Section: Human Neuroblastoma Culture Cells and Human T Lymphocytes Ismentioning

confidence: 99%

Autumnalamide targeted proteins of the immunophilin family

et al. 2017

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Previous works with autumnalamide reported that Store Operated Calcium (SOC) channels were blocked through mitochondrial modulation. In the present paper we studied the effect of autumnalamide on ionomycin Ca fluxes. Thus, autumnalamide did not modify ionomycin-sensitive intracellular pools while the ionomycin-induced Ca influx was blocked with similar potency whether the incubation was done before or after ionomycin-sensitive pools depletion. Nevertheless, autumnalamide was not able to inhibit ionomycin-induced Ca influx once the membrane channels were activated. Moreover, the compound efficiently inhibited flufenamic acid (FFA) Ca release induced in this organelle but no the next influx. Since in previous work the effect of autumnalamide was inhibited by cyclosporine A (CsA), structures that target this drug were studied. Therefore, the affinity of autumnalamide for cyclophilin D (Cyp D) was examined. The K obtained for Cyp D- autumnalamide was 1.51±1.399. Moreover, the K for Cyp A- autumnalamide was calculated. The peptide had a similar order of Cyp A binding affinity than CsA (8.08±1.23 and 6.85±1.1μM respectively). After testing autumnalamide-binding capacity for Cyp A, the activity of this compound on Cyp A pathway was tested. Thus, the effect on interleukin (IL)-2 release on activated T-lymphocytes was checked. Autumnalamide was able to reduce IL-2 levels near to T cells in resting conditions. Next, the effect over calcineurin and NFATc1 was also evaluated. While CsA inhibits both calcineurin and NFATc1, autumnalamide did not produce any effect. From these results we can conclude that, autumnalamide targeted mitochondrion and prevent T-cells from IL-2 production through the modulation of SOC Ca channels.

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“…Since it has been shown that the initial elevation of calcium evoked by PRL arises from the influx of calcium (Alfonso et al 2001), calcium accumulation was determined by measuring the uptake of 45 Ca from the medium. Mammary explants were cultured in 3 ml medium containing 45 Ca (10 µCi/ ml) and [ 3 H]inulin (5 µCi/ml).…”

Section: Calcium Accumulationmentioning

confidence: 99%

Prolactin activation of mammary nitric oxide synthase: molecular mechanisms

Ff¹

2002

Journal of Molecular Endocrinology

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Prolactin (PRL) is capable of stimulating both calcium and nitric oxide (NO) accumulation in mammary epithelial cells within 15 min. A calcium ionophore was also able to stimulate NO levels to an extent similar to that generated by PRL. Furthermore, maximal concentrations of PRL and the ionophore were not additive, suggesting that they were both using the same pathway, i.e. calcium. Finally, the depletion of intracellular calcium completely abrogated the effect of PRL on NO production. No other pathway known to affect NO synthase (NOS) influenced the action of PRL. Specifically, manipulations of protein phosphatase 2B, protein kinase B (PKB), protein kinase C (PKC), and arginine transport did not alter the activation of NOS by PRL. Therefore, the ability of PRL to stimulate NO production at 15 min can be completely explained by its ability to elevate intracellular calcium.

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Prolactin induces calcium influx and release from intracellular pools in human T lymphocytes by activation of tyrosine kinases

Cited by 6 publications

References 23 publications

Spongionella Secondary Metabolites, Promising Modulators of Immune Response through CD147 Receptor Modulation

Spongionella Secondary Metabolites, Promising Modulators of Immune Response through CD147 Receptor Modulation

Autumnalamide targeted proteins of the immunophilin family

Prolactin activation of mammary nitric oxide synthase: molecular mechanisms

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