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.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Cell Adhesion Molecules/*metabolism ; Dopamine/*analogs & derivatives ; Histocompatibility Antigens Class II/*metabolism ; Human Umbilical Vein Endothelial Cells/*metabolism ; Interferon-gamma/*pharmacology ; Lymphocyte Activation/*drug effects ; T-Lymphocytes/*immunology; Antigens, Differentiation, B-Lymphocyte/metabolism ; Cell Adhesion/drug effects ; Dopamine/pharmacology ; Gene Expression Regulation/drug effects ; HLA-DR Antigens/metabolism ; Human Umbilical Vein Endothelial Cells/drug effects ; Humans ; Integrin alpha4beta1/metabolism ; Intercellular Adhesion Molecule-1/metabolism ; Lymphocyte Function-Associated Antigen-1/metabolism ; Nuclear Proteins/metabolism ; Signal Transduction/drug effects ; T-Lymphocytes/drug effects ; Trans-Activators/metabolism ; Vascular Cell Adhesion Molecule-1/metabolism

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.

Am J Transplant. 2018 Feb;18(2):293-307. (PMID: 29243394)
J Leukoc Biol. 2014 Sep;96(3):453-62. (PMID: 24929005)
J Exp Med. 1992 Jan 1;175(1):305-8. (PMID: 1730925)
Am J Transplant. 2010 Sep;10(9):2066-73. (PMID: 20883541)
Nat Immunol. 2004 Jul;5(7):661-9. (PMID: 15224091)
Cell. 1995 Jul 14;82(1):155-65. (PMID: 7606781)
Transplant Rev (Orlando). 2015 Jul;29(3):109-13. (PMID: 25576467)
Physiol Res. 2017 May 4;66(2):167-180. (PMID: 27982677)
Am J Transplant. 2004 Jan;4(1):22-30. (PMID: 14678031)
Am J Transplant. 2015 Nov;15(11):2921-30. (PMID: 26096305)
Am J Transplant. 2007 Mar;7(3):518-26. (PMID: 17352710)
Br J Pharmacol. 2010 Aug;160(8):1857-71. (PMID: 20649585)
Immunol Today. 1990 Mar;11(3):83-8. (PMID: 2186745)
Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3150-4. (PMID: 2014234)
Cochrane Database Syst Rev. 2017 Jul 21;7:CD006750. (PMID: 28730648)
J Interferon Res. 1986 Jun;6(3):267-79. (PMID: 2427623)
Nature. 2016 Jun 30;534(7609):710-3. (PMID: 27350246)
PLoS One. 2012;7(5):e36408. (PMID: 22574154)
Nat Immunol. 2002 Feb;3(2):151-8. (PMID: 11812992)
Transpl Int. 2016 Sep;29(9):974-84. (PMID: 26563531)
Curr Opin Organ Transplant. 2015 Apr;20(2):152-8. (PMID: 25719899)
J Pharmacol Exp Ther. 2014 Jan;348(1):77-85. (PMID: 24135075)
Am J Transplant. 2004 Mar;4(3):378-83. (PMID: 14961990)
PLoS One. 2013 Sep 02;8(9):e73122. (PMID: 24023820)
Transplantation. 2006 Mar 15;81(5):643-54. (PMID: 16534463)
J Immunol. 1996 May 1;156(9):3174-83. (PMID: 8617938)
Nucleic Acids Res. 2005 Nov 10;33(20):e175. (PMID: 16284200)
Nature. 1992 Dec 3;360(6403):474-7. (PMID: 1448172)
Pharmacol Res. 2018 Feb;128:252-263. (PMID: 29113759)
J Med Chem. 2016 Nov 10;59(21):9855-9865. (PMID: 27731639)
Nature. 1990 Jun 14;345(6276):615-8. (PMID: 2190094)
Transplantation. 2008 Aug 15;86(3):371-6. (PMID: 18698238)
Transplantation. 2016 Jan;100(1):80-90. (PMID: 26674731)
Am J Transplant. 2009 Aug;9(8):1859-67. (PMID: 19563338)
Clin J Am Soc Nephrol. 2009 Feb;4(2):481-508. (PMID: 19218475)
Am J Transplant. 2018 Feb;18(2):364-376. (PMID: 29194971)
J Exp Med. 2002 Sep 2;196(5):679-91. (PMID: 12208882)
Am J Transplant. 2017 Jul;17(7):1802-1812. (PMID: 28117941)
Transplantation. 2011 Mar 27;91(6):657-65. (PMID: 21242883)
Cell. 1995 Feb 10;80(3):413-22. (PMID: 7532110)
Kidney Int. 1996 Feb;49(2):518-24. (PMID: 8821839)
Nat Immunol. 2011 Dec 25;13(2):129-35. (PMID: 22197977)
PLoS One. 2012;7(8):e43525. (PMID: 22916273)
J Immunol. 2004 Feb 15;172(4):2341-51. (PMID: 14764703)
J Immunol. 2010 Apr 15;184(8):4205-14. (PMID: 20231691)
Am J Transplant. 2019 Jan;19(1):277-284. (PMID: 30253052)
PLoS One. 2014 Jun 13;9(6):e99298. (PMID: 24926788)
Transplant Rev (Orlando). 2017 Jan;31(1):10-17. (PMID: 28340885)
Planta Med. 2016 Jun;82(9-10):903-9. (PMID: 27135626)
Intensive Care Med. 1996 Dec;22(12):1424-32. (PMID: 8986499)
Transplantation. 2015 May;99(5):935-41. (PMID: 25675202)

0 (Antigens, Differentiation, B-Lymphocyte)
0 (Cell Adhesion Molecules)
0 (HLA-DR Antigens)
0 (Histocompatibility Antigens Class II)
0 (Integrin alpha4beta1)
0 (Lymphocyte Function-Associated Antigen-1)
0 (MHC class II transactivator protein)
0 (N-octanoyldopamine)
0 (Nuclear Proteins)
0 (Trans-Activators)
0 (Vascular Cell Adhesion Molecule-1)
0 (invariant chain)
126547-89-5 (Intercellular Adhesion Molecule-1)
82115-62-6 (Interferon-gamma)
VTD58H1Z2X (Dopamine)

Date Created: 20191220 Date Completed: 20201109 Latest Revision: 20210110

20221213

PMC6920350

10.1038/s41598-019-55983-1

31853095