Ouabain Modulates Zymosan-Induced Peritonitis in Mice

  • Mediators Inflamm. 2015:2015:265798. doi: 10.1155/2015/265798.
Jacqueline Alves Leite  1 Anne Kaliery De Abreu Alves  2 José Guilherme Marques Galvão  2 Mariana Pires Teixeira  3 Luiz Henrique Agra Cavalcante-Silva  2 Cristoforo Scavone  1 Alexandre Morrot  4 Vivian Mary Rumjanek  3 Sandra Rodrigues-Mascarenhas  5
Affiliations
  • 1. Instituto de Ciências Biomédicas, Departamento de Farmacologia, Laboratório de Neurofarmacologia Molecular, Universidade de São Paulo, 05508-900 São Paulo, SP, Brazil.
  • 2. Centro de Biotecnologia, Laboratório de Imunofarmacologia, Programa de Pós-Graduação em Fisiologia Multicêntrico, Universidade Federal da Paraíba, 58059-900 João Pessoa, PB, Brazil.
  • 3. Instituto de Bioquímica Médica Leopoldo de Meis, Laboratório de Imunologia Tumoral, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro, RJ, Brazil.
  • 4. Laboratório de Biologia do Sistema Imune, Instituto de Microbiologia, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro, RJ, Brazil.
  • 5. Centro de Biotecnologia, Laboratório de Imunofarmacologia, Programa de Pós-Graduação em Fisiologia Multicêntrico, Universidade Federal da Paraíba, 58059-900 João Pessoa, PB, Brazil ; Centro de Ciências da Saúde, Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos, Universidade Federal da Paraíba, 58059-900 João Pessoa, PB, Brazil.
Abstract

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.