Ouabain Modulates Zymosan-Induced Peritonitis in Mice

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. Thu...

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Main Authors: Jacqueline Alves Leite, Anne Kaliery De Abreu Alves, José Guilherme Marques Galvão, Mariana Pires Teixeira, Luiz Henrique Agra Cavalcante-Silva, Cristoforo Scavone, Alexandre Morrot, Vivian Mary Rumjanek, Sandra Rodrigues-Mascarenhas
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2015/265798
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author Jacqueline Alves Leite
Anne Kaliery De Abreu Alves
José Guilherme Marques Galvão
Mariana Pires Teixeira
Luiz Henrique Agra Cavalcante-Silva
Cristoforo Scavone
Alexandre Morrot
Vivian Mary Rumjanek
Sandra Rodrigues-Mascarenhas
author_facet Jacqueline Alves Leite
Anne Kaliery De Abreu Alves
José Guilherme Marques Galvão
Mariana Pires Teixeira
Luiz Henrique Agra Cavalcante-Silva
Cristoforo Scavone
Alexandre Morrot
Vivian Mary Rumjanek
Sandra Rodrigues-Mascarenhas
author_sort Jacqueline Alves Leite
collection DOAJ
description 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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spelling doaj-art-f2278b2a920e426994a96e9de42505fa2025-02-03T05:47:31ZengWileyMediators of Inflammation0962-93511466-18612015-01-01201510.1155/2015/265798265798Ouabain Modulates Zymosan-Induced Peritonitis in MiceJacqueline Alves Leite0Anne Kaliery De Abreu Alves1José Guilherme Marques Galvão2Mariana Pires Teixeira3Luiz Henrique Agra Cavalcante-Silva4Cristoforo Scavone5Alexandre Morrot6Vivian Mary Rumjanek7Sandra Rodrigues-Mascarenhas8Instituto de Ciências Biomédicas, Departamento de Farmacologia, Laboratório de Neurofarmacologia Molecular, Universidade de São Paulo, 05508-900 São Paulo, SP, BrazilCentro de Biotecnologia, Laboratório de Imunofarmacologia, Programa de Pós-Graduação em Fisiologia Multicêntrico, Universidade Federal da Paraíba, 58059-900 João Pessoa, PB, BrazilCentro de Biotecnologia, Laboratório de Imunofarmacologia, Programa de Pós-Graduação em Fisiologia Multicêntrico, Universidade Federal da Paraíba, 58059-900 João Pessoa, PB, BrazilInstituto de Bioquímica Médica Leopoldo de Meis, Laboratório de Imunologia Tumoral, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro, RJ, BrazilCentro de Biotecnologia, Laboratório de Imunofarmacologia, Programa de Pós-Graduação em Fisiologia Multicêntrico, Universidade Federal da Paraíba, 58059-900 João Pessoa, PB, BrazilInstituto de Ciências Biomédicas, Departamento de Farmacologia, Laboratório de Neurofarmacologia Molecular, Universidade de São Paulo, 05508-900 São Paulo, SP, BrazilLaboratório de Biologia do Sistema Imune, Instituto de Microbiologia, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro, RJ, BrazilInstituto de Bioquímica Médica Leopoldo de Meis, Laboratório de Imunologia Tumoral, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro, RJ, BrazilCentro de Biotecnologia, Laboratório de Imunofarmacologia, Programa de Pós-Graduação em Fisiologia Multicêntrico, Universidade Federal da Paraíba, 58059-900 João Pessoa, PB, BrazilOuabain, 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.http://dx.doi.org/10.1155/2015/265798
spellingShingle Jacqueline Alves Leite
Anne Kaliery De Abreu Alves
José Guilherme Marques Galvão
Mariana Pires Teixeira
Luiz Henrique Agra Cavalcante-Silva
Cristoforo Scavone
Alexandre Morrot
Vivian Mary Rumjanek
Sandra Rodrigues-Mascarenhas
Ouabain Modulates Zymosan-Induced Peritonitis in Mice
Mediators of Inflammation
title Ouabain Modulates Zymosan-Induced Peritonitis in Mice
title_full Ouabain Modulates Zymosan-Induced Peritonitis in Mice
title_fullStr Ouabain Modulates Zymosan-Induced Peritonitis in Mice
title_full_unstemmed Ouabain Modulates Zymosan-Induced Peritonitis in Mice
title_short Ouabain Modulates Zymosan-Induced Peritonitis in Mice
title_sort ouabain modulates zymosan induced peritonitis in mice
url http://dx.doi.org/10.1155/2015/265798
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