title: The influence of Ouabain on human dendritic cells maturation.
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.
authors.affiliation: Instituto 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.
authors.forename: C R
authors.initials: CR
authors.lastname: Nascimento
authors.affiliation: Instituto 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.
authors.forename: R C
authors.initials: RC
authors.lastname: Valente
authors.affiliation: Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, 21 941-902 Rio de Janeiro, RJ, Brazil.
authors.forename: J
authors.initials: J
authors.lastname: Echevarria-Lima
authors.affiliation: Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, 21 941-902 Rio de Janeiro, RJ, Brazil.
authors.forename: C F L
authors.initials: CF
authors.lastname: Fontes
authors.affiliation: Instituto de Biologia, Universidade Federal Fluminense, 24 230-340 Niterói, RJ, Brazil.
authors.forename: L
authors.initials: L
authors.lastname: de Araujo-Martins
authors.affiliation: Instituto de Biologia, Universidade Federal Fluminense, 24 230-340 Niterói, RJ, Brazil.
authors.forename: E G
authors.initials: EG
authors.lastname: Araujo
authors.affiliation: Laboratorio 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, Brazil.
authors.forename: V M
authors.initials: VM
authors.lastname: Rumjanek
mesh_terms: D051940:B7-2 Antigen / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects*; D004705:Endocytosis; D004791:Enzyme Inhibitors / Q000737:chemistry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D015847:Interleukin-4 / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology; D016328:NF-kappa B / Q000378:metabolism; D010042:Ouabain / Q000737:chemistry*; D010641:Phenotype; D017452:Receptors, IgG / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D051940:B7-2 Antigen; D016207:Cytokines; D004791:Enzyme Inhibitors; D006684:HLA-DR Antigens; C508598:IL4 protein, human; D018950:Lipopolysaccharide Receptors; D016328:NF-kappa B; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D010042:Ouabain; D016178:Granulocyte-Macrophage Colony-Stimulating Factor