The Influence of Ouabain on Human Dendritic Cells Maturation

Nascimento, Christine Rabello; Valente, Raphael C; Echevarria-Lima, Juliana; Fontes, Carlos Frederico Leite; Araujo-Martins, Leandro de; Araújo, Elizabeth Giestal de; Rumjanek, Vivian M.

doi:10.1155/2014/494956

Cited by 10 publications

(6 citation statements)

References 54 publications

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“…In the present study, when ouabain was associated with zymosan it significantly decreased the NF- κ B activation observed with zymosan alone. However, similar to a study using dendritic cells [ 16 ] ouabain by itself was capable of increasing NF- κ B activation. Therefore, the decrease in TNF- α and IL-1 β levels observed by us correlates with an inhibitory effect of ouabain on NF- κ B binding activity.…”

Section: Discussionsupporting

confidence: 71%

“…The combination of ouabain plus corticoids produced a synergic effect inducing thymic atrophy in vivo [ 14 ]. Additionally, ouabain was shown to modulate function and cytokine production of monocytes in vitro [ 15 ] and dendritic cells [ 16 ]. Ouabain negatively modulated acute peritoneal inflammatory response induced by Leishmania amazonensis infection in Swiss mice [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

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Ouabain Modulates Zymosan‐Induced Peritonitis in Mice

Leite

Alves

Galvão

et al. 2015

Mediators of Inflammation

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Ouabain, a potent inhibitor of the Na+, K+-ATPase, was identified as an endogenous substance. Recently, ouabain was shown to affect various immunological processes. We have previously demonstrated the ability of ouabain to modulate inflammation, but little is known about the mechanisms involved. Thus, the aim of the present work is to evaluate the immune modulatory role of ouabain on zymosan-induced peritonitis in mice. Our results show that ouabain decreased plasma exudation (33%). After induction of inflammation, OUA treatment led to a 46% reduction in the total number of cells, as a reflex of a decrease of polymorphonuclear leukocytes, which does not appear to be due to cell death. Furthermore, OUA decreased TNF-α (57%) and IL-1β (58%) levels, without interfering with IL-6 and IL-10. Also, in vitro experiments show that ouabain did not affect endocytic capacity. Moreover, electrophoretic mobility shift assay (EMSA) shows that zymosan treatment increased (85%) NF-κB binding activity and that ouabain reduced (30%) NF-κB binding activity induced by zymosan. Therefore, our data suggest that ouabain modulated acute inflammatory response, reducing the number of cells and cytokines levels in the peritoneal cavity, as well as NFκB activation, suggesting a new mode of action of this substance.

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Section: Discussionsupporting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Ouabain Modulates Zymosan‐Induced Peritonitis in Mice

Leite

Alves

Galvão

et al. 2015

Mediators of Inflammation

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show abstract

“…The influence of ouabain on DC was also described. Nascimento et al ( 2014 ) demonstrated that ouabain modulates dendritic cells markers and IL-12 production during activation by TNF-α. Additionally, ouabain affects monocyte/macrophage activation (Sowa and Przewłocki, 1997 ; Teixeira and Rumjanek, 2014 ).…”

Section: Ouabain and Immune Systemmentioning

confidence: 99%

Much More than a Cardiotonic Steroid: Modulation of Inflammation by Ouabain

et al. 2017

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Since the discovery of ouabain as a cardiotonic steroid hormone present in higher mammals, research about it has progressed rapidly and several of its physiological and pharmacological effects have been described. Ouabain can behave as a stress hormone and adrenal cortex is its main source. Direct effects of ouabain are originated due to the binding to its receptor, the Na+/K+-ATPase, on target cells. This interaction can promote Na+ transport blockade or even activation of signaling transduction pathways (e.g., EGFR/Src-Ras-ERK pathway activation), independent of ion transport. Besides the well-known effect of ouabain on the cardiovascular system and blood pressure control, compelling evidence indicates that ouabain regulates a number of immune functions. Inflammation is a tightly coordinated immunological function that is also affected by ouabain. Indeed, this hormone can modulate many inflammatory events such as cell migration, vascular permeability, and cytokine production. Moreover, ouabain also interferes on neuroinflammation. However, it is not clear how ouabain controls these events. In this brief review, we summarize the updates of ouabain effect on several aspects of peripheral and central inflammation, bringing new insights into ouabain functions on the immune system.

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“…However, they could clearly demonstrate that ouabain does not influence these cells. Nascimento et al [71] were the first to investigate the action of ouabain (100 nM) on human dendritic cells (DCs). Interestingly, the TNF-induced expression of CD83 and the production of IL-12, two features of DC maturation, were reduced by ouabain, whereas the capability of DCs to activate lymphocytes remained unaltered.…”

Section: Neutrophils Natural Killer Cells and Dendritic Cellsmentioning

confidence: 99%

New Knowledge About Old Drugs: The Anti-Inflammatory Properties of Cardiac Glycosides

2017

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In the 19th century, cardio-active steroid glycosides, shortly cardiac glycosides, were scientifically established as drugs against heart failure. Their in vivo, cellular, and molecular actions as well as their predominant target, Na+-K+-ATPase, have been comprehensively investigated in the 20th century and the discovery of endogenous cardiac glycosides has fostered this research field. In the last years, however, results from clinical trials and meta-analyses have questioned their therapeutic value due to efficacy and safety issues. This has led to a considerable decline of their usage. Beyond the cardiovascular system, cardiac glycosides have been increasingly recognized as antitumor compounds and Na+-K+-ATPase has evolved into a promising drug target in oncology. A wealth of review articles exists that intensively discuss these topics. Surprisingly, the anti-inflammatory actions of cardiac glycosides, which were discovered in the 1960s, have so far hardly been perceived and have not yet been summarized. This review provides an overview of the in vivo and in vitro actions of cardiac glycosides on inflammatory processes and of the signaling mechanisms responsible for these effects: cardiac glycosides have been found to decrease inflammatory symptoms in different animal models of acute and chronic inflammation. Regarding the underlying mechanisms most research has focused on leukocytes. In these cells, cardiac glycosides primarily inhibit cell proliferation and the secretion of proinflammatory cytokines.

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The Influence of Ouabain on Human Dendritic Cells Maturation

Cited by 10 publications

References 54 publications

Ouabain Modulates Zymosan‐Induced Peritonitis in Mice

Ouabain Modulates Zymosan‐Induced Peritonitis in Mice

Much More than a Cardiotonic Steroid: Modulation of Inflammation by Ouabain

New Knowledge About Old Drugs: The Anti-Inflammatory Properties of Cardiac Glycosides

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