The MEK Inhibitor Trametinib Suppresses Major Histocompatibility Antigen-mismatched Rejection Following Pancreatic Islet Transplantation.
Journal
Transplantation direct
ISSN: 2373-8731
Titre abrégé: Transplant Direct
Pays: United States
ID NLM: 101651609
Informations de publication
Date de publication:
Sep 2020
Sep 2020
Historique:
received:
22
01
2020
revised:
19
06
2020
accepted:
04
07
2020
entrez:
28
8
2020
pubmed:
28
8
2020
medline:
28
8
2020
Statut:
epublish
Résumé
Potential adverse effects, such as functional impairment of islets, render conventional immunosuppressive drugs unsuitable for use in islet transplantation. In addition, as a single therapy, they cannot prolong islet allograft survival. Here, we investigated the utility of the mitogen-activated protein kinase inhibitor trametinib and asked whether it ameliorates acute rejection of transplanted islets without the need for conventional immunosuppressants. Islets from fully major histocompatibility complex-mismatched BALB/c mice were transplanted into streptozotocin-induced diabetic C57BL/6 mice via the portal vein. These mice received trametinib or vehicle (orally) for 28 days. Isolated islets from BALB/c mice were incubated in vitro with different concentrations of trametinib to determine viability and function. Trametinib (0.1 and 0.3 mg/kg) prolonged graft survival significantly ( Trametinib delayed islet graft rejection by inhibiting functional differentiation of naive CD4
Sections du résumé
BACKGROUND
BACKGROUND
Potential adverse effects, such as functional impairment of islets, render conventional immunosuppressive drugs unsuitable for use in islet transplantation. In addition, as a single therapy, they cannot prolong islet allograft survival. Here, we investigated the utility of the mitogen-activated protein kinase inhibitor trametinib and asked whether it ameliorates acute rejection of transplanted islets without the need for conventional immunosuppressants.
METHODS
METHODS
Islets from fully major histocompatibility complex-mismatched BALB/c mice were transplanted into streptozotocin-induced diabetic C57BL/6 mice via the portal vein. These mice received trametinib or vehicle (orally) for 28 days. Isolated islets from BALB/c mice were incubated in vitro with different concentrations of trametinib to determine viability and function.
RESULTS
RESULTS
Trametinib (0.1 and 0.3 mg/kg) prolonged graft survival significantly (
CONCLUSIONS
CONCLUSIONS
Trametinib delayed islet graft rejection by inhibiting functional differentiation of naive CD4
Identifiants
pubmed: 32851124
doi: 10.1097/TXD.0000000000001045
pmc: PMC7423917
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e591Informations de copyright
Copyright © 2020 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.
Déclaration de conflit d'intérêts
The authors declare no conflicts of interest.
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