Document Detail


Impact of small molecules immunosuppressants on p-glycoprotein activity and T-cell function.
MedLine Citation:
PMID:  22974789     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
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 drugs. 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 uptake, efflux and kinetic of extrusion in CD4+ and CD8+ subsets by flow cytometry. Antigen-specific memory T-cell 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 significantly 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. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
Authors:
Inés Llaudó; Linda Cassis; Joan Torras; Oriol Bestard; Marcel la Franquesa; Josep M Cruzado; Gema Cerezo; Esther Castaño; Jordi Petriz; Immaculada Herrero-Fresneda; Josep M Grinyó; Núria Lloberas
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Société canadienne des sciences pharmaceutiques     Volume:  15     ISSN:  1482-1826     ISO Abbreviation:  J Pharm Pharm Sci     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-09-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9807281     Medline TA:  J Pharm Pharm Sci     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  407-19     Citation Subset:  IM    
Affiliation:
Nephrology Department and Laboratory of Experimental Nephrology, Bellvitge University Hospital, Hospitalet de Llobregat.
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