title: The trophic effect of ouabain on retinal ganglion cells is mediated by IL-1β and TNF-α.
abstract: Ouabain is a steroid hormone that binds to the enzyme Na(+), K(+) - ATPase and stimulates different intracellular pathways controlling growth, proliferation and cell survival. IL-1β and TNF-α are pleiotropic molecules, conventionally regarded as pro-inflammatory cytokines with well-known effects in the immune system. In addition, IL-1β and TNF-α also play important roles in the nervous system including neuroprotective effects. Previous data from our group showed that ouabain treatment is able to induce an increase in retinal ganglion cell survival kept in mixed retinal cell cultures. The aim of this work was to investigate if IL-1β and TNF-α could be mediating the trophic effect of ouabain on retinal ganglion cells. Our results show that the trophic effect of ouabain on retinal ganglion cell was inhibited by either anti-IL-1β or anti-TNF-α antibodies. In agreement, IL-1β or TNF-α increased the retinal ganglion cells survival in a dose-dependent manner. Accordingly, ouabain treatment induces a temporal release of TNF-α and IL-1β from retinal cell cultures. Interestingly, TNF-α and IL-1β regulate each other intracellular levels. Our results suggest that ouabain treatment triggers the activation of TNF-α and IL-1β signaling pathways leading to an increase in retinal ganglion cell survival.
authors.affiliation: Departamento de Neurobiologia, Programa de Neurociências, Outeiro de São João Batista s/n CEP: 24020-150, Universidade Federal Fluminense, Niterói, RJ, Brazil.
authors.forename: Juliana
authors.initials: J
authors.lastname: Salles von-Held-Ventura
authors.affiliation: Departamento de Neurobiologia, Programa de Neurociências, Outeiro de São João Batista s/n CEP: 24020-150, Universidade Federal Fluminense, Niterói, RJ, Brazil.
authors.forename: Thalita
authors.initials: T
authors.lastname: Mázala-de-Oliveira
authors.affiliation: Departamento de Neurobiologia, Programa de Neurociências, Outeiro de São João Batista s/n CEP: 24020-150, Universidade Federal Fluminense, Niterói, RJ, Brazil.
authors.forename: Amanda
authors.initials: A
authors.lastname: Cândida da Rocha Oliveira
authors.affiliation: Departamento de Neurobiologia, Programa de Neurociências, Outeiro de São João Batista s/n CEP: 24020-150, Universidade Federal Fluminense, Niterói, RJ, Brazil.
authors.forename: Marcelo Gomes
authors.initials: MG
authors.lastname: Granja
authors.affiliation: Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Departamento de Fisiologia e Farmacodinâmica, Av., no 4365, Manguinhos, 21045-900, Rio de Janeiro, RJ, Brazil.
authors.forename: Cassiano Felippe
authors.initials: CF
authors.lastname: Gonçalves-de-Albuquerque
authors.affiliation: Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Departamento de Fisiologia e Farmacodinâmica, Av., no 4365, Manguinhos, 21045-900, Rio de Janeiro, RJ, Brazil.
authors.forename: Hugo Caire
authors.initials: HC
authors.lastname: Castro-Faria-Neto
authors.affiliation: Departamento de Neurobiologia, Programa de Neurociências, Outeiro de São João Batista s/n CEP: 24020-150, Universidade Federal Fluminense, Niterói, RJ, Brazil. Electronic address: egiestal@vm.uff.br.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Giestal-de-Araujo
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D018836:Inflammation Mediators / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology*; D010042:Ouabain / Q000008:administration & dosage*; D051381:Rats; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D018836:Inflammation Mediators; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D010042:Ouabain
keywords: Cell culture; Pro-inflammatory cytokines; Retina and rat; Steroid hormone