Título:
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Impact of small molecules immunosuppressants on P-glycoprotein activity and T-cell function
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Autor/a:
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Llaudó Vallmajor, Inés; Cassis, L.; Torras Ambròs, Joan; Bestard Matamoros, Oriol; Franquesa, Marcella; Cruzado, Josep Ma.; Cerezo, Gema; Castaño Boldú, Esther; Pétriz, J.; Herrero Fresneda, Immaculada; Grinyó Boira, Josep M.; Lloberas Blanch, Núria
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Otros autores:
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Universitat de Barcelona |
Abstract:
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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. |
Materia(s):
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-Immunosupressió -Transport biològic -Proteïnes de membrana -Immunosuppression -Biological transport -Membrane proteins |
Derechos:
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cc-by-sa (c) Llaudó, I. et al., 2012
http://creativecommons.org/licenses/by-sa/3.0/es |
Tipo de documento:
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Artículo Artículo - Versión publicada |
Editor:
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Canadian Society for Pharmaceutical Sciences
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