N-Octanoyl-Dopamine inhibits cytokine production in activated T-cells and diminishes MHC-class-II expression as well as adhesion molecules in IFN gamma-stimulated endothelial cells

Bjorn B. Hofmann, Nicolas Krapp, Yingchun Li, Carolina De La Torre, Marloes Sol, Jana D. Braun, Matthias Kolibabka, Prama Pallavi, Bernhard K. Kraemer, Benito A. Yard*, Anna-Isabelle Kaelsch

*Corresponding author for this work

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    Abstract

    IFN gamma enhances allograft immunogenicity and facilitates T-cell mediated rejection. This may cause interstitial fibrosis and tubular atrophy (IFTA), contributing to chronic allograft loss. We assessed if inhibition of T-cell activation by N-octanoyl dopamine (NOD) impairs adherence of activated T-cells to endothelial cells and the ability of activated T-cells to produce IFN gamma. We also assessed if NOD affects IFN gamma mediated gene expression in endothelial cells. The presence of NOD during T-cell activation significantly blunted their adhesion to unstimulated and cytokine stimulated HUVEC. Supernatants of these T-cells displayed significantly lower concentrations of TNF alpha and IFN gamma and were less capable to facilitate T-cell adhesion. In the presence of NOD VLA-4 (CD49d/CD29) and LFA-1 (CD11a/CD18) expression on T-cells was reduced. NOD treatment of IFN gamma stimulated HUVEC reduced the expression of MHC class II transactivator (CIITA), of MHC class II and its associated invariant chain CD74. Since IFTA is associated with T-cell mediated rejection and IFN gamma to a large extent regulates immunogenicity of allografts, our current data suggest a potential clinical use of NOD in the treatment of transplant recipients. Further in vivo studies are warranted to confirm these in vitro findings and to assess the benefit of NOD on IFTA in clinically relevant models.

    Original languageEnglish
    Article number19338
    Number of pages11
    JournalScientific Reports
    Volume9
    DOIs
    Publication statusPublished - 18-Dec-2019

    Keywords

    • HLA-DR MOLECULES
    • KIDNEY-TRANSPLANTATION
    • BRAIN-DEATH
    • REJECTION
    • IMMUNOSUPPRESSION
    • PROLIFERATION
    • INFLAMMATION
    • PRESERVATION
    • ELIMINATION
    • GENERATION

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