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Updated: Apr 18, 2026
Development and Functional Characterization of Murine Tolerogenic Dendritic Cells
Published on: May 18, 2018
The influence of Ouabain on human dendritic cells maturation
C R Nascimento1, R C Valente1, J Echevarria-Lima2
1Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, 21 941-902 Rio de Janeiro, RJ, Brazil ; Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21 941-902 Rio de Janeiro, RJ, Brazil.
Abstract:
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.
Insights
Ouabain, a known Na,K-ATPase inhibitor, influences immune cells. This study reveals Ouabain alters dendritic cell (DC) maturation, affecting immune responses and potentially balancing immunity and tolerance.
Area of Science:
- Immunology
- Cell Biology
- Pharmacology
Background:
- Ouabain (Oua) is recognized as a Na,K-ATPase inhibitor with diverse cellular effects.
- Previous research indicates Ouabain impacts lymphocyte proliferation, apoptosis, and monocyte differentiation.
- The specific effects of Ouabain on dendritic cells (DCs) remain largely unexplored.
Purpose of the Study:
- To investigate the influence of Ouabain on dendritic cell (DC) maturation and function.
- To determine how Ouabain affects key markers of DC activation and immune signaling.
Main Methods:
- Immature DCs were generated from human monocytes cultured with IL-4 and GM-CSF.
- DCs were stimulated with TNF-α in the presence or absence of Ouabain (100 nM) for 48 hours.
- Expression of maturation markers (CD83, HLA-DR, CD86, CD80), IL-12 production, and antigen capture were analyzed.
Main Results:
- Ouabain abolished TNF-α-induced CD83 expression and IL-12 production in DCs.
- TNF-α-induced downregulation of antigen capture was observed even with Ouabain treatment.
- Ouabain increased HLA-DR and CD86 expression while maintaining CD80 levels.
- DC capacity to activate lymphocytes was not altered by Ouabain.
Conclusions:
- Ouabain induces a distinct maturation profile in dendritic cells.
- These Ouabain-modified DCs may play a role in modulating the balance between immune activation and tolerance.
- Further research is warranted to elucidate the precise immunological consequences of Ouabain-induced DC alterations.
