title: Fluoxetine suppresses calcium signaling in human T lymphocytes through depletion of intracellular calcium stores.
abstract: Selective serotonin reuptake inhibitors, such as fluoxetine, have recently been shown to exert anti-inflammatory and immunosuppressive effects. Although the effects on cytokine secretion, proliferation and viability of T lymphocytes have been extensively characterized, little is known about the mechanism behind these effects. It is well known that Ca(2+) signaling is an important step in the signaling transduction pathway following T cell receptor activation. Therefore, we investigated if fluoxetine interferes with Ca(2+) signaling in Jurkat T lymphocytes. Fluoxetine was found to suppress Ca(2+) signaling in response to T cell receptor activation. Moreover, fluoxetine was found to deplete intracellular Ca(2+) stores, thereby leaving less Ca(2+) available for release upon IP3- and ryanodine-receptor activation. The Ca(2+)-modifying effects of fluoxetine are not related to its capability to block the serotonin transporter, as even a large excess of 5HT did not abolish the effects. In conclusion, these data show that fluoxetine decreases IP3- and ryanodine-receptor mediated Ca(2+) release in Jurkat T lymphocytes, an effect likely to be at the basis of the observed immunosuppression.
authors.affiliation: Laboratory of Pharmaceutical Biotechnology, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.
authors.forename: V
authors.initials: V
authors.lastname: Gobin
authors.affiliation: Physiology Group, Department of Basic Medical Sciences, Ghent University, Ghent, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: De Bock
authors.affiliation: Laboratory of Pharmaceutical Biotechnology, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.
authors.forename: B J G
authors.initials: BJ
authors.lastname: Broeckx
authors.affiliation: Department of Internal Medicine, Ghent University, Ghent, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Kiselinova
authors.affiliation: Department of Internal Medicine, Ghent University, Ghent, Belgium.
authors.forename: W
authors.initials: W
authors.lastname: De Spiegelaere
authors.affiliation: Department of Internal Medicine, Ghent University, Ghent, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Vandekerckhove
authors.affiliation: Laboratory of Pharmaceutical Biotechnology, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Van Steendam
authors.affiliation: Physiology Group, Department of Basic Medical Sciences, Ghent University, Ghent, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Leybaert
authors.affiliation: Laboratory of Pharmaceutical Biotechnology, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium. Electronic address: Dieter.Deforce@Ugent.be.
authors.forename: D
authors.initials: D
authors.lastname: Deforce
mesh_terms: D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D003593:Cytoplasm / Q000378:metabolism; D005473:Fluoxetine / Q000494:pharmacology*; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
chemical_list: D002118:Calcium; D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Calcium signaling; Fluoxetine; Insitol 1,4,5-trisphosphate; Ryanodine receptor; SSRI; T lymphocyte