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Title: Impact of small molecules immunosuppressants on P-glycoprotein activity and T-cell function
Author: Llaudó Vallmajor, Inés
Cassis, L.
Torras Ambròs, Joan
Bestard Matamoros, Oriol
Franquesa, Marcella
Cruzado, Josep Ma.
Cerezo, Gema
Castaño Boldú, Esther
Pétriz, Jordi
Herrero Fresneda, Immaculada
Grinyó Boira, Josep M.
Lloberas Blanch, Núria
Keywords: Immunosupressió
Transport biològic
Proteïnes de membrana
Biological transport
Membrane proteins
Issue Date: 15-Jul-2012
Publisher: Canadian Society for Pharmaceutical Sciences
Abstract: Purpose. 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.
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It is part of: Journal of Pharmacy and Pharmaceutical Sciences, 2012, vol. 15, num. 3, p. 407-419
ISSN: 1482-1826
Appears in Collections:Articles publicats en revistes (Ciències Clíniques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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