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J Leukoc Biol. 2014 Sep;96(3):453-62. doi: 10.1189/jlb.3A0813-455R. Epub 2014 Jun 13.

N-Octanoyl dopamine transiently inhibits T cell proliferation via G1 cell-cycle arrest and inhibition of redox-dependent transcription factors.

Author information

1
Departments of Medicine, Nephrology, Endocrinology, Diabetology, Rheumatology and.
2
Anesthesia and Critical Care, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; and.
3
Department of Pathology and Medical Biology, Pathology Section, University of Groningen, University Medical Center, Groningen, The Netherlands.
4
Departments of Medicine, Nephrology, Endocrinology, Diabetology, Rheumatology and benito.yard@medma.uni-heidelberg.de.

Abstract

Recently, we developed a nonhemodynamic dopamine derivative, NOD, which has profound anti-inflammatory effects in vitro. As NOD also protects rats from ischemic AKI, the present study tested whether NOD is able to modulate cellular immunity for potential use as a T cell-suppressive agent. To this end, T cells were stimulated by anti-CD3/CD28 or PMA/ionomycin in the presence or absence of different concentrations of NOD. T cell proliferation, activation markers, intracellular cytokine expression, and activation of transcription factors were assessed. Whereas T cell proliferation was inhibited significantly by NOD at Day 3, proliferation was restored at Day 7 or later depending on the NOD concentration used. Inhibition of proliferation was reflected by a diminished CD25 expression and switch from naive to memory T cells. Early TCR activation events were unaffected, yet NF-κB and AP-1 were strongly inhibited by NOD. The inhibitory effect of NOD seemed to be dependent on its redox activity, as NOT, a redox-inactive NOD derivate, did not influence proliferation. NOD displayed synergistic effects with CNIs on T cell proliferation. Our data demonstrate that NOD displays T cell-suppressive activity. In keeping with its anti-inflammatory action and its beneficial effect on ischemia-induced AKI, NOD may be an interesting drug candidate to prevent CNI-related side-effects.

KEYWORDS:

AP-1; N-acyl dopamine; NF-κB; T lymphocytes; immunosuppression; transplantation

PMID:
24929005
PMCID:
PMC5395937
DOI:
10.1189/jlb.3A0813-455R
[Indexed for MEDLINE]
Free PMC Article

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