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dc.contributor.authorLlaudó Vallmajor, Inés-
dc.contributor.authorCassis, L.-
dc.contributor.authorTorras Ambròs, Joan-
dc.contributor.authorBestard Matamoros, Oriol-
dc.contributor.authorFranquesa, Marcella-
dc.contributor.authorCruzado, Josep Ma.-
dc.contributor.authorCerezo, Gema-
dc.contributor.authorCastaño Boldú, Esther-
dc.contributor.authorPétriz, Jordi-
dc.contributor.authorHerrero Fresneda, Immaculada-
dc.contributor.authorGrinyó Boira, Josep M.-
dc.contributor.authorLloberas Blanch, Núria-
dc.description.abstractPurpose. P-glycoprotein (Pgp) is a member of the ABC-transporter family that transports substances across cellular membranes acting as an efflux pump extruding drugs out of the cells. Pgp plays a key role on the pharmacokinetics of several dr ugs. Herein, we have studied the effects of immunosuppressants on Pgp function, assessing rhodamine-123 (Rho123) uptake and efflux in different T- cell subsets. Methods. Different immunosuppressants such as Cyclosporine (CsA), Rapamycin (Rapa) and Tacrolimus (Tac) were used to assess the in vitro effect on Pgp function of main T-cell subsets among healthy volunteers. We measured Rho123 upta ke, efflux and kinetic of extrusion in CD4 + and CD8 + subsets by flow cytometry. Antigen-specific memory T-ce ll responses were assessed by measuring T-cell proliferation and cytokine secretion using an allogeneic mixed lymphocyte reaction. Results. Rho123 uptake in groups treated with CsA and CsA+Rapa was signif icantly decreased compared to non-treated group and the other immunosupressants in both T cells subsets. Pgp activity was also reduced in CsA and CsA+Rapa compared to the other immunosupressants but it was only significant in the CsA group for CD8 + subset. Kinetic extrusion of Rho123 by Pgp in all groups was faster in CD8 + T cells. All immunosuppressants and the specific Pgp inhibitor PSC833 diminished antigen-primed T-cell proliferation, especially CD8 + T-cell subset. Conclusions. Our data indicate that small molecules immunosuppressants, especially CsA, inhibit Pgp activity and T-cell function being the CD8 + T cells more susceptible to this effect. These findings support the importance of Pgp when designing combined immunosuppressive regimens.-
dc.format.extent13 p.-
dc.publisherCanadian Society for Pharmaceutical Sciences-
dc.relation.isformatofReproducció del document publicat a:
dc.relation.ispartofJournal of Pharmacy and Pharmaceutical Sciences, 2012, vol. 15, num. 3, p. 407-419-
dc.rightscc-by-sa (c) Llaudó, I. et al., 2012-
dc.subject.classificationTransport biològic-
dc.subject.classificationProteïnes de membrana-
dc.subject.otherBiological transport-
dc.subject.otherMembrane proteins-
dc.titleImpact of small molecules immunosuppressants on P-glycoprotein activity and T-cell function-
Appears in Collections:Articles publicats en revistes (Ciències Clíniques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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