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Treatment with Tacrolimus and Sirolimus Reveals No Additional Adverse Effects on Human Islets In Vitro Compared to Each Drug Alone but They Are Reduced by Adding Glucocorticoids

Tacrolimus and sirolimus are important immunosuppressive drugs used in human islet transplantation; however, they are linked to detrimental effects on islets and reduction of long-term graft function. Few studies investigate the direct effects of these drugs combined in parallel with single drug exp...

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Autores principales: Kloster-Jensen, Kristine, Sahraoui, Afaf, Vethe, Nils Tore, Korsgren, Olle, Bergan, Stein, Foss, Aksel, Scholz, Hanne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4739465/
https://www.ncbi.nlm.nih.gov/pubmed/26885529
http://dx.doi.org/10.1155/2016/4196460
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author Kloster-Jensen, Kristine
Sahraoui, Afaf
Vethe, Nils Tore
Korsgren, Olle
Bergan, Stein
Foss, Aksel
Scholz, Hanne
author_facet Kloster-Jensen, Kristine
Sahraoui, Afaf
Vethe, Nils Tore
Korsgren, Olle
Bergan, Stein
Foss, Aksel
Scholz, Hanne
author_sort Kloster-Jensen, Kristine
collection PubMed
description Tacrolimus and sirolimus are important immunosuppressive drugs used in human islet transplantation; however, they are linked to detrimental effects on islets and reduction of long-term graft function. Few studies investigate the direct effects of these drugs combined in parallel with single drug exposure. Human islets were treated with or without tacrolimus (30 μg/L), sirolimus (30 μg/L), or a combination thereof for 24 hrs. Islet function as well as apoptosis was assessed by glucose-stimulated insulin secretion (GSIS) and Cell Death ELISA. Proinflammatory cytokines were analysed by qRT-PCR and Bio-Plex. Islets exposed to the combination of sirolimus and tacrolimus were treated with or without methylprednisolone (1000 μg/L) and the expression of the proinflammatory cytokines was investigated. We found the following: (i) No additive reduction in function and viability in islets existed when tacrolimus and sirolimus were combined compared to the single drug. (ii) Increased expression of proinflammatory cytokines mRNA and protein levels in islets took place. (iii) Methylprednisolone significantly decreased the proinflammatory response in islets induced by the drug combination. Although human islets are prone to direct toxic effect of tacrolimus and sirolimus, we found no additive effects of the drug combination. Short-term exposure of glucocorticoids could effectively reduce the proinflammatory response in human islets induced by the combination of tacrolimus and sirolimus.
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spelling pubmed-47394652016-02-16 Treatment with Tacrolimus and Sirolimus Reveals No Additional Adverse Effects on Human Islets In Vitro Compared to Each Drug Alone but They Are Reduced by Adding Glucocorticoids Kloster-Jensen, Kristine Sahraoui, Afaf Vethe, Nils Tore Korsgren, Olle Bergan, Stein Foss, Aksel Scholz, Hanne J Diabetes Res Research Article Tacrolimus and sirolimus are important immunosuppressive drugs used in human islet transplantation; however, they are linked to detrimental effects on islets and reduction of long-term graft function. Few studies investigate the direct effects of these drugs combined in parallel with single drug exposure. Human islets were treated with or without tacrolimus (30 μg/L), sirolimus (30 μg/L), or a combination thereof for 24 hrs. Islet function as well as apoptosis was assessed by glucose-stimulated insulin secretion (GSIS) and Cell Death ELISA. Proinflammatory cytokines were analysed by qRT-PCR and Bio-Plex. Islets exposed to the combination of sirolimus and tacrolimus were treated with or without methylprednisolone (1000 μg/L) and the expression of the proinflammatory cytokines was investigated. We found the following: (i) No additive reduction in function and viability in islets existed when tacrolimus and sirolimus were combined compared to the single drug. (ii) Increased expression of proinflammatory cytokines mRNA and protein levels in islets took place. (iii) Methylprednisolone significantly decreased the proinflammatory response in islets induced by the drug combination. Although human islets are prone to direct toxic effect of tacrolimus and sirolimus, we found no additive effects of the drug combination. Short-term exposure of glucocorticoids could effectively reduce the proinflammatory response in human islets induced by the combination of tacrolimus and sirolimus. Hindawi Publishing Corporation 2016 2016-01-18 /pmc/articles/PMC4739465/ /pubmed/26885529 http://dx.doi.org/10.1155/2016/4196460 Text en Copyright © 2016 Kristine Kloster-Jensen et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Kloster-Jensen, Kristine
Sahraoui, Afaf
Vethe, Nils Tore
Korsgren, Olle
Bergan, Stein
Foss, Aksel
Scholz, Hanne
Treatment with Tacrolimus and Sirolimus Reveals No Additional Adverse Effects on Human Islets In Vitro Compared to Each Drug Alone but They Are Reduced by Adding Glucocorticoids
title Treatment with Tacrolimus and Sirolimus Reveals No Additional Adverse Effects on Human Islets In Vitro Compared to Each Drug Alone but They Are Reduced by Adding Glucocorticoids
title_full Treatment with Tacrolimus and Sirolimus Reveals No Additional Adverse Effects on Human Islets In Vitro Compared to Each Drug Alone but They Are Reduced by Adding Glucocorticoids
title_fullStr Treatment with Tacrolimus and Sirolimus Reveals No Additional Adverse Effects on Human Islets In Vitro Compared to Each Drug Alone but They Are Reduced by Adding Glucocorticoids
title_full_unstemmed Treatment with Tacrolimus and Sirolimus Reveals No Additional Adverse Effects on Human Islets In Vitro Compared to Each Drug Alone but They Are Reduced by Adding Glucocorticoids
title_short Treatment with Tacrolimus and Sirolimus Reveals No Additional Adverse Effects on Human Islets In Vitro Compared to Each Drug Alone but They Are Reduced by Adding Glucocorticoids
title_sort treatment with tacrolimus and sirolimus reveals no additional adverse effects on human islets in vitro compared to each drug alone but they are reduced by adding glucocorticoids
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4739465/
https://www.ncbi.nlm.nih.gov/pubmed/26885529
http://dx.doi.org/10.1155/2016/4196460
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