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

Autor: Hofmann BB; Department of Nephrology, Endocrinology and Rheumatology, Fifth Department of Medicine, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany., Krapp N; Department of Nephrology, Endocrinology and Rheumatology, Fifth Department of Medicine, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany., Li Y; Department of Nephrology, Endocrinology and Rheumatology, Fifth Department of Medicine, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany., De La Torre C; Center of Medical Research, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany., Sol M; Department of Medical Biology and Pathology, University Medical Center Groningen, Groningen, Netherlands., Braun JD; Department of Nephrology, Endocrinology and Rheumatology, Fifth Department of Medicine, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany., Kolibabka M; Department of Nephrology, Endocrinology and Rheumatology, Fifth Department of Medicine, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany., Pallavi P; Department of Nephrology, Endocrinology and Rheumatology, Fifth Department of Medicine, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany., Krämer BK; Department of Nephrology, Endocrinology and Rheumatology, Fifth Department of Medicine, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany., Yard BA; Department of Nephrology, Endocrinology and Rheumatology, Fifth Department of Medicine, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany. benito.yard@medma.uni-heidelberg.de., Kälsch AI; Department of Nephrology, Endocrinology and Rheumatology, Fifth Department of Medicine, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2019 Dec 18; Vol. 9 (1), pp. 19338. Date of Electronic Publication: 2019 Dec 18.
DOI: 10.1038/s41598-019-55983-1
Abstrakt: IFNγ 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 IFNγ. We also assessed if NOD affects IFNγ 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 TNFα and IFNγ 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 IFNγ 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 IFNγ 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.
Databáze: MEDLINE
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