The Influence of Ouabain on Human Dendritic Cells Maturation

Although known as a Na,K-ATPase inhibitor, several other cellular and systemic actions have been ascribed to the steroid Ouabain (Oua). Particularly in the immune system, our group showed that Ouabain acts on decreasing lymphocyte proliferation, synergizing with glucocorticoids in spontaneous thymoc...

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Main Authors: C. R. Nascimento, R. C. Valente, J. Echevarria-Lima, C. F. L. Fontes, L. de Araujo-Martins, E. G. Araujo, V. M. Rumjanek
Format: Article
Language:English
Published: Wiley 2014-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2014/494956
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author C. R. Nascimento
R. C. Valente
J. Echevarria-Lima
C. F. L. Fontes
L. de Araujo-Martins
E. G. Araujo
V. M. Rumjanek
author_facet C. R. Nascimento
R. C. Valente
J. Echevarria-Lima
C. F. L. Fontes
L. de Araujo-Martins
E. G. Araujo
V. M. Rumjanek
author_sort C. R. Nascimento
collection DOAJ
description Although known as a Na,K-ATPase inhibitor, several other cellular and systemic actions have been ascribed to the steroid Ouabain (Oua). Particularly in the immune system, our group showed that Ouabain acts on decreasing lymphocyte proliferation, synergizing with glucocorticoids in spontaneous thymocyte apoptosis, and also lessening CD14 expression and blocking CD16 upregulation on human monocytes. However, Ouabain effects on dendritic cells (DCs) were not explored so far. Considering the peculiar plasticity and the importance of DCs in immune responses, the aim of our study was to investigate DC maturation under Ouabain influence. To generate immature DCs, human monocytes were cultured with IL-4 and GM-CSF (5 days). To investigate Ouabain role on DC activation, DCs were stimulated with TNF-α for 48 h in the presence or absence of Ouabain. TNF-induced CD83 expression and IL-12 production were abolished in DCs incubated with 100 nM Ouabain, though DC functional capacity concerning lymphocyte activation remained unaltered. Nevertheless, TNF-α-induced antigen capture downregulation, another maturation marker, occurred even in the presence of Ouabain. Besides, Ouabain increased HLA-DR and CD86 expression, whereas CD80 expression was maintained. Collectively, our results suggest that DCs respond to Ouabain maturating into a distinct category, possibly contributing to the balance between immunity and tolerance.
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spelling doaj-art-17e0fc83478f4361b860ec079ee54f332025-02-03T01:00:26ZengWileyMediators of Inflammation0962-93511466-18612014-01-01201410.1155/2014/494956494956The Influence of Ouabain on Human Dendritic Cells MaturationC. R. Nascimento0R. C. Valente1J. Echevarria-Lima2C. F. L. Fontes3L. de Araujo-Martins4E. G. Araujo5V. M. Rumjanek6Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, 21 941-902 Rio de Janeiro, RJ, BrazilInstituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, 21 941-902 Rio de Janeiro, RJ, BrazilInstituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, 21 941-902 Rio de Janeiro, RJ, BrazilInstituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, 21 941-902 Rio de Janeiro, RJ, BrazilInstituto de Biologia, Universidade Federal Fluminense, 24 230-340 Niterói, RJ, BrazilInstituto de Biologia, Universidade Federal Fluminense, 24 230-340 Niterói, RJ, BrazilLaboratorio de Imunologia Tumoral, Instituto de Bioquímica Médica Leopoldo de Meis, Centro de Ciencias da Saude, Bloco H02, Sala 003, Universidade Federal do Rio de Janeiro, 21 941-902 Rio de Janeiro, RJ, BrazilAlthough known as a Na,K-ATPase inhibitor, several other cellular and systemic actions have been ascribed to the steroid Ouabain (Oua). Particularly in the immune system, our group showed that Ouabain acts on decreasing lymphocyte proliferation, synergizing with glucocorticoids in spontaneous thymocyte apoptosis, and also lessening CD14 expression and blocking CD16 upregulation on human monocytes. However, Ouabain effects on dendritic cells (DCs) were not explored so far. Considering the peculiar plasticity and the importance of DCs in immune responses, the aim of our study was to investigate DC maturation under Ouabain influence. To generate immature DCs, human monocytes were cultured with IL-4 and GM-CSF (5 days). To investigate Ouabain role on DC activation, DCs were stimulated with TNF-α for 48 h in the presence or absence of Ouabain. TNF-induced CD83 expression and IL-12 production were abolished in DCs incubated with 100 nM Ouabain, though DC functional capacity concerning lymphocyte activation remained unaltered. Nevertheless, TNF-α-induced antigen capture downregulation, another maturation marker, occurred even in the presence of Ouabain. Besides, Ouabain increased HLA-DR and CD86 expression, whereas CD80 expression was maintained. Collectively, our results suggest that DCs respond to Ouabain maturating into a distinct category, possibly contributing to the balance between immunity and tolerance.http://dx.doi.org/10.1155/2014/494956
spellingShingle C. R. Nascimento
R. C. Valente
J. Echevarria-Lima
C. F. L. Fontes
L. de Araujo-Martins
E. G. Araujo
V. M. Rumjanek
The Influence of Ouabain on Human Dendritic Cells Maturation
Mediators of Inflammation
title The Influence of Ouabain on Human Dendritic Cells Maturation
title_full The Influence of Ouabain on Human Dendritic Cells Maturation
title_fullStr The Influence of Ouabain on Human Dendritic Cells Maturation
title_full_unstemmed The Influence of Ouabain on Human Dendritic Cells Maturation
title_short The Influence of Ouabain on Human Dendritic Cells Maturation
title_sort influence of ouabain on human dendritic cells maturation
url http://dx.doi.org/10.1155/2014/494956
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