Inhibition of Nuclear Translocation of Calcineurin Suppresses T-Cell Activation and Prevents Acute Rejection of Donor Hearts

Panther, Franziska; Strasen, Jörn; Czolbe, Martin; Lazariotou, Maria; Burkard, Natalie; Williams, Tatjana; Lange, Volkmar; Otto, Christoph; Ritter, Oliver

doi:10.1097/tp.0b013e3182090f67

Transplantation

2011

DOI: 10.1097/tp.0b013e3182090f67

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Inhibition of Nuclear Translocation of Calcineurin Suppresses T-Cell Activation and Prevents Acute Rejection of Donor Hearts

Franziska Panther

Jörn Strasen²,

Martin Czolbe³

et al.

Abstract: Inhibition of nuclear translocation of CnA is a novel approach to inhibit the activation of the CnA/NFAT signaling cascade. Further studies have to demonstrate the long-term use of this principle in vivo.

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Cited by 7 publications

References 17 publications

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Carvacrol ameliorates skin allograft rejection through modulating macrophage polarization by activating the Wnt signalling pathway

Zhao,

Tang,

Liang

et al. 2024

Phytotherapy Research

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Post‐transplantation immune rejection remains an important factor for transplant patients. However, conventional immunosuppressants are associated with substantial adverse effects. Natural immunosuppressants present a promising alternative to conventional counterparts, boasting exceptional biological activity, minimal toxicity and reduced side effects. We identified carvacrol as a prospective immunosuppressive agent following T cell proliferation experiment and validated carvacrol's immunosuppressive efficacy in the murine allogeneic skin graft model. T cell proliferation assay was used to screen natural small molecule compounds and the immunosuppressive effect of compounds was evaluated in MHC‐mismatched murine allogeneic skin graft model. H&E and immunohistochemical staining were applied to evaluate the pathological grade. Furthermore, flow cytometry was uitlized to analyse the immunophenotype changes of immune cells. Western blotting and q‐PCR were used to detect the expression of key molecules in macrophages. In vitro, carvacrol demonstrates significant inhibition of the proliferation of CD4+ T and CD8+ T cells. It notably reduces inflammatory factor expression within the allografts, suppresses T cell differentiation toward Th1 phenotype and expansion. Furthermore, carvacrol prominently hinders M1‐type macrophages polarization by activating Wnt signaling. Notably, the anti‐rejection efficacy of carvacrol was significantly weakened upon the removal of macrophages in mice using chlorophosphate liposomes. Carvacrol could significantly inhibit T cell proliferation, alleviate graft rejection and has outstanding toxicological safety. The molecular mechanism of the anti‐rejection effect of carvacrol is closely related to its mediating activation of macrophage Wnt pathway, inhibiting M1 polarization and inducing T cell differentiation.

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Carvacrol ameliorates skin allograft rejection through modulating macrophage polarization by activating the Wnt signalling pathway

Zhao,

Tang,

Liang

et al. 2024

Phytotherapy Research

View full text Add to dashboard Cite

show abstract

The PI3Kδ selective inhibitor AS2541019 suppresses donor-specific antibody production in rat cardiac and non-human primate renal allotransplant models

Marui

Fukahori

Ito

et al. 2019

International Immunopharmacology

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Establishment of a novel volume-loaded heterotopic heart transplantation model in rats

Wang

Zhang

et al. 2013

Journal of Surgical Research

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Inhibition of Nuclear Translocation of Calcineurin Suppresses T-Cell Activation and Prevents Acute Rejection of Donor Hearts

Abstract: Inhibition of nuclear translocation of CnA is a novel approach to inhibit the activation of the CnA/NFAT signaling cascade. Further studies have to demonstrate the long-term use of this principle in vivo.

Cited by 7 publications

References 17 publications

Carvacrol ameliorates skin allograft rejection through modulating macrophage polarization by activating the Wnt signalling pathway

Carvacrol ameliorates skin allograft rejection through modulating macrophage polarization by activating the Wnt signalling pathway

The PI3Kδ selective inhibitor AS2541019 suppresses donor-specific antibody production in rat cardiac and non-human primate renal allotransplant models

Establishment of a novel volume-loaded heterotopic heart transplantation model in rats

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