Open AccessInhibition of nuclear translocation of calcineurin suppresses T-cell activation and prevents acute rejection of donor hearts.
Author(s) -
Franziska Panther,
Jörn Strasen,
Martin Czolbe,
Maria Lazariotou,
Natalie Burkard,
Tatjana Williams,
Volkmar Lange,
Christoph Otto,
Oliver Ritter
Publication year - 2011
Publication title -
transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.45
H-Index - 204
eISSN - 1534-6080
pISSN - 0041-1337
DOI - 10.1097/tp.0b013e3182090f67
Subject(s) - nfat , calcineurin , jurkat cells , t cell , dephosphorylation , in vivo , microbiology and biotechnology , cytosol , phosphatase , cd8 , chromosomal translocation , biology , in vitro , chemistry , transplantation , immunology , antigen , biochemistry , immune system , medicine , phosphorylation , enzyme , gene
Inhibition of calcineurin (CnA) activity by cyclosporine A (CsA) is the mainstay in immunosuppressive therapy. CsA inhibits the phosphatase activity of the cytosolic phosphatase CnA and, therefore, prevents the dephosphorylation and subsequently nuclear translocation of the transcription factor nuclear factor of activated T cells (NFAT). However, CsA has multiple other targets within the cell and is, therefore, not specific. We developed a new approach to inhibit CnA/NFAT signaling. This synthetic peptide prevented CnA nuclear translocation in vitro. The purpose of this study was to demonstrate that this novel approach could potentially inhibit T-cell function in vitro and in vivo.