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Published in: Inflammation Research 12/2017

01-12-2017 | Original Research Paper

Ouabain attenuates ovalbumin-induced airway inflammation

Authors: José Guilherme F. M. Galvão, Luiz Henrique Agra Cavalcante-Silva, Deyse Cristina M. Carvalho, Laércia Karla D. P. Ferreira, Talissa Mozzini Monteiro, Adriano Francisco Alves, Larissa Adilis M. P. Ferreira, Francisco Allysson A. F. Gadelha, Marcia Regina Piuvezam, Sandra Rodrigues-Mascarenhas

Published in: Inflammation Research | Issue 12/2017

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Abstract

Purpose

Ouabain, an Na+/K+-ATPase inhibitor hormone, presents immunomodulatory actions, including anti-inflammatory effect on acute inflammation models.

Methods

In the present study, the effect of ouabain in a model of allergic airway inflammation induced by ovalbumin (OVA) was assessed.

Results

Initially, it was observed that ouabain treatment inhibited cellular migration induced by OVA on bronchoalveolar lavage fluid (BALF), mostly granulocytes, without modulating macrophage migration. In addition, it was observed, by flow cytometry, that ouabain reduces CD3high lymphocytes cells on BALF. Furthermore, treatment with ouabain decreased IL-4 and IL-13 levels on BALF. Ouabain also promoted pulmonary histological alterations, including decreased cell migration into peribronchiolar and perivascular areas, and reduced mucus production in bronchioles regions observed through hematoxylin–eosin (HE) and by periodic acid-Schiff stain, respectively. Allergic airway inflammation is characterized by high OVA-specific IgE serum titer. This parameter was also reduced by the treatment with ouabain.

Conclusions

Therefore, our data demonstrate that ouabain negatively modulates allergic airway inflammation induced by OVA.
Literature
2.
go back to reference Erdmann E, Schoner W. Ouabain-receptor interactions in (Na+K+)-ATPase preparations from different tissues and species determination of kinetic constants and dissociation constants. BBA Biomembr. 1973;307:386–98. doi:10.1007/BF00501108.CrossRef Erdmann E, Schoner W. Ouabain-receptor interactions in (Na+K+)-ATPase preparations from different tissues and species determination of kinetic constants and dissociation constants. BBA Biomembr. 1973;307:386–98. doi:10.​1007/​BF00501108.CrossRef
8.
go back to reference Tymiak AA, Norman JA, Bolgar M, DiDonato GC, Lee H, Parker WL, et al. Physicochemical characterization of a ouabain isomer isolated from bovine hypothalamus. Proc Natl Acad Sci USA. 1993;90:8189–93.CrossRefPubMedPubMedCentral Tymiak AA, Norman JA, Bolgar M, DiDonato GC, Lee H, Parker WL, et al. Physicochemical characterization of a ouabain isomer isolated from bovine hypothalamus. Proc Natl Acad Sci USA. 1993;90:8189–93.CrossRefPubMedPubMedCentral
12.
16.
go back to reference Szamel M, Schneider S, Resch K. Functional interrelationship between Na+/K+-ATPase and lysolecithin acyltransferase in plasma membranes of mitogen-stimulated rabbit thymocytes. J Biol Chem. 1981;256:9198–204.PubMed Szamel M, Schneider S, Resch K. Functional interrelationship between Na+/K+-ATPase and lysolecithin acyltransferase in plasma membranes of mitogen-stimulated rabbit thymocytes. J Biol Chem. 1981;256:9198–204.PubMed
18.
go back to reference Valente RC, Nascimento CR, Araujo EG, Rumjanek VM. mCD14 expression in human monocytes is downregulated by ouabain via transactivation of epithelial growth factor receptor and activation of p38 mitogen-activated protein kinase. Neuroimmunomodulation. 2009;16:228–36. doi:10.1159/000212383.CrossRefPubMed Valente RC, Nascimento CR, Araujo EG, Rumjanek VM. mCD14 expression in human monocytes is downregulated by ouabain via transactivation of epithelial growth factor receptor and activation of p38 mitogen-activated protein kinase. Neuroimmunomodulation. 2009;16:228–36. doi:10.​1159/​000212383.CrossRefPubMed
19.
go back to reference Teixeira MP, Rumjanek VM. Ouabain affects the expression of activation markers, cytokine production, and endocytosis of human monocytes. Mediat Inflamm. 2014. doi:10.1155/2014/760368. Teixeira MP, Rumjanek VM. Ouabain affects the expression of activation markers, cytokine production, and endocytosis of human monocytes. Mediat Inflamm. 2014. doi:10.​1155/​2014/​760368.
20.
go back to reference Nascimento CR, Valente RC, Echevarria-Lima J, Fontes CF, de Araujo-Martins L, Araujo EG, et al. The influence of ouabain on human dendritic cells maturation. Mediat Inflamm. 2014. doi:10.1155/2014/494956. Nascimento CR, Valente RC, Echevarria-Lima J, Fontes CF, de Araujo-Martins L, Araujo EG, et al. The influence of ouabain on human dendritic cells maturation. Mediat Inflamm. 2014. doi:10.​1155/​2014/​494956.
21.
go back to reference Rodrigues-Mascarenhas S, Echevarria-Lima J, Fernandes dos Santos N, Rumjanek VM. CD69 expression induced by thapsigargin, phorbol ester and ouabain on thymocytes is dependent on external Ca2+ entry. Life Sci. 2003;73:1037–51. doi:10.1016/S0024-3205(03)00377-1.CrossRefPubMed Rodrigues-Mascarenhas S, Echevarria-Lima J, Fernandes dos Santos N, Rumjanek VM. CD69 expression induced by thapsigargin, phorbol ester and ouabain on thymocytes is dependent on external Ca2+ entry. Life Sci. 2003;73:1037–51. doi:10.​1016/​S0024-3205(03)00377-1.CrossRefPubMed
23.
24.
go back to reference De Vasconcelos DI, Leite JA, Carneiro LT, Piuvezam MR, de Lima MR, de Morais LC, et al. Anti-inflammatory and antinociceptive activity of ouabain in mice. Mediat Inflamm. 2011. doi:10.1155/2011/912925. De Vasconcelos DI, Leite JA, Carneiro LT, Piuvezam MR, de Lima MR, de Morais LC, et al. Anti-inflammatory and antinociceptive activity of ouabain in mice. Mediat Inflamm. 2011. doi:10.​1155/​2011/​912925.
25.
go back to reference Leite JA, Alves AK, Galvão JGFM, Teixeira MP, Cavalcante-Silva LHA, Scavone C, et al. Ouabain modulates zymosan-induced peritonitis in mice. Mediat Inflamm. 2015. doi:10.1155/2015/265798. Leite JA, Alves AK, Galvão JGFM, Teixeira MP, Cavalcante-Silva LHA, Scavone C, et al. Ouabain modulates zymosan-induced peritonitis in mice. Mediat Inflamm. 2015. doi:10.​1155/​2015/​265798.
28.
31.
37.
go back to reference Vieira GC, De Lima JF, De Figueiredo RC, Mascarenhas SR, Bezerra-Santos CR, Piuvezam MR. Inhaled Cissampelos sympodialis down-regulates airway allergic reaction by reducing lung CD3+ T cells. Phytother Res. 2012;27:916–25. doi:10.1002/ptr.4791.CrossRefPubMed Vieira GC, De Lima JF, De Figueiredo RC, Mascarenhas SR, Bezerra-Santos CR, Piuvezam MR. Inhaled Cissampelos sympodialis down-regulates airway allergic reaction by reducing lung CD3+ T cells. Phytother Res. 2012;27:916–25. doi:10.​1002/​ptr.​4791.CrossRefPubMed
38.
go back to reference Holt PG, Rose AH, Batty JE, Turner KJ. Introduction of adjuvant-independent IgE responses in inbred mice: primary, secondary and persistent IgE responses to ovalbumin and ovomucoid. Int Arch Allergy Appl Immunol. 1981;65:42–50. doi:10.1159/000232736.CrossRefPubMed Holt PG, Rose AH, Batty JE, Turner KJ. Introduction of adjuvant-independent IgE responses in inbred mice: primary, secondary and persistent IgE responses to ovalbumin and ovomucoid. Int Arch Allergy Appl Immunol. 1981;65:42–50. doi:10.​1159/​000232736.CrossRefPubMed
39.
40.
go back to reference Venkayya R, Lam M, Willkom M, Grünig G, Corry DB, Erle DJ. The Th2 lymphocyte products IL-4 and IL-13 rapidly induce airway hyperresponsiveness through direct effects on resident airway cells. Am J Respir Cell Mol Biol. 2002;26:202–8. doi:10.1165/ajrcmb.26.2.4600.CrossRefPubMed Venkayya R, Lam M, Willkom M, Grünig G, Corry DB, Erle DJ. The Th2 lymphocyte products IL-4 and IL-13 rapidly induce airway hyperresponsiveness through direct effects on resident airway cells. Am J Respir Cell Mol Biol. 2002;26:202–8. doi:10.​1165/​ajrcmb.​26.​2.​4600.CrossRefPubMed
42.
go back to reference Cowden JM, Riley JP, Ma JY, Thurmond RL, Dunford PJ. Histamine H4 receptor antagonism diminishes existing airway inflammation and dysfunction via modulation of Th2 cytokines. Respir Res. 2010;11:1–12. doi:10.1186/1465-9921-11-86.CrossRef Cowden JM, Riley JP, Ma JY, Thurmond RL, Dunford PJ. Histamine H4 receptor antagonism diminishes existing airway inflammation and dysfunction via modulation of Th2 cytokines. Respir Res. 2010;11:1–12. doi:10.​1186/​1465-9921-11-86.CrossRef
43.
45.
go back to reference Ninsontia C, Chanvorachote P. Ouabain mediates integrin switch in human lung cancer cells. Anticancer Res. 2014;34:5495–502.PubMed Ninsontia C, Chanvorachote P. Ouabain mediates integrin switch in human lung cancer cells. Anticancer Res. 2014;34:5495–502.PubMed
46.
go back to reference Takada Y, Matsuo K, Ogura H, Bai L, Toki A, Wang L, et al. Odoroside A and ouabain inhibit Na+/K+-ATPase and prevent NF-kappaB-inducible protein expression by blocking Na+-dependent amino acid transport. Biochem Pharmacol. 2009;78:1157–66. doi:10.1016/j.bcp.2009.06.027.CrossRefPubMed Takada Y, Matsuo K, Ogura H, Bai L, Toki A, Wang L, et al. Odoroside A and ouabain inhibit Na+/K+-ATPase and prevent NF-kappaB-inducible protein expression by blocking Na+-dependent amino acid transport. Biochem Pharmacol. 2009;78:1157–66. doi:10.​1016/​j.​bcp.​2009.​06.​027.CrossRefPubMed
49.
go back to reference Gonçalves-de-Albuquerque CF, Burth P, Silva AR, de Moraes IM, Oliveira FM, Santelli RE, et al. Murine lung injury caused by Leptospira interrogans glycolipoprotein, a specific Na/K-ATPase inhibitor. Respir Res. 2014;15:1–12. doi:10.1186/s12931-014-0093-2.CrossRef Gonçalves-de-Albuquerque CF, Burth P, Silva AR, de Moraes IM, Oliveira FM, Santelli RE, et al. Murine lung injury caused by Leptospira interrogans glycolipoprotein, a specific Na/K-ATPase inhibitor. Respir Res. 2014;15:1–12. doi:10.​1186/​s12931-014-0093-2.CrossRef
50.
go back to reference Azzawi M, Johnston PW, Majumdar S, Kay AB, Jeffery PK. T lymphocytes and activated eosinophils in airway mucosa in fatal asthma and cystic fibrosis. Am Rev Respir Dis. 1992;145:1477–82.CrossRefPubMed Azzawi M, Johnston PW, Majumdar S, Kay AB, Jeffery PK. T lymphocytes and activated eosinophils in airway mucosa in fatal asthma and cystic fibrosis. Am Rev Respir Dis. 1992;145:1477–82.CrossRefPubMed
51.
go back to reference Bystrom J, Amin K, Bishop-Bailey D. Analysing the eosinophil cationic protein—a clue to the function of the eosinophil granulocyte. Respir Res. 2011;12:1465–9921.CrossRef Bystrom J, Amin K, Bishop-Bailey D. Analysing the eosinophil cationic protein—a clue to the function of the eosinophil granulocyte. Respir Res. 2011;12:1465–9921.CrossRef
53.
go back to reference Carlson M, Peterson C, Venge P. The influence of IL-3, IL-5, and GM-CSF on normal human eosinophil and neutrophil C3b induced degranulation. Allergy. 1993;48:437–42.PubMed Carlson M, Peterson C, Venge P. The influence of IL-3, IL-5, and GM-CSF on normal human eosinophil and neutrophil C3b induced degranulation. Allergy. 1993;48:437–42.PubMed
56.
go back to reference Mattila PS, Ullman KS, Fiering S, et al. The action of cyclosporin A and FK506 suggest a novel step in the activation of T lymphocytes. EMBO J. 1990;9:4425–33.PubMedPubMedCentral Mattila PS, Ullman KS, Fiering S, et al. The action of cyclosporin A and FK506 suggest a novel step in the activation of T lymphocytes. EMBO J. 1990;9:4425–33.PubMedPubMedCentral
57.
go back to reference Rao A, Luo C, Hogan PG. Transcription factors of the NFAT family: regulation and function. Annu Rev Immunol. 1997;15:707–47.CrossRefPubMed Rao A, Luo C, Hogan PG. Transcription factors of the NFAT family: regulation and function. Annu Rev Immunol. 1997;15:707–47.CrossRefPubMed
60.
go back to reference Corry DB, Folkesson HG, Warnock ML, Erle DJ, Matthay MA, Wiener-Kronish JP, et al. Interleukin 4, but not interleukin 5 or eosinophils, is required in a murine model of acute airway hyperreactivity. J Exp Med. 1996;183:109–17. doi:10.1084/jem.183.1.109.CrossRefPubMed Corry DB, Folkesson HG, Warnock ML, Erle DJ, Matthay MA, Wiener-Kronish JP, et al. Interleukin 4, but not interleukin 5 or eosinophils, is required in a murine model of acute airway hyperreactivity. J Exp Med. 1996;183:109–17. doi:10.​1084/​jem.​183.​1.​109.CrossRefPubMed
64.
go back to reference Huang TJ, MacAry P, Eynott P, et al. Allergen-specific Th1 cells counteract effecrent Th2 cell-dependent bronchial hyperresponsiveness and eosinophilic inflammation, partly via IFN-g. J Immunol. 2001;166:207–17.CrossRefPubMed Huang TJ, MacAry P, Eynott P, et al. Allergen-specific Th1 cells counteract effecrent Th2 cell-dependent bronchial hyperresponsiveness and eosinophilic inflammation, partly via IFN-g. J Immunol. 2001;166:207–17.CrossRefPubMed
65.
go back to reference Cohn L, Homer RJ, Niu N, Bottomly K. T helper 1 cells and interferon gamma regulate allergic airway inflammation and mucus production. J Exp Med. 1999;190:1309–18.CrossRefPubMedPubMedCentral Cohn L, Homer RJ, Niu N, Bottomly K. T helper 1 cells and interferon gamma regulate allergic airway inflammation and mucus production. J Exp Med. 1999;190:1309–18.CrossRefPubMedPubMedCentral
66.
go back to reference Boumpas DT, Chrousos GP, Wilder RL, Cupps TR, Balow JE. Glucocorticoid therapy for immune-mediated diseases: basic and clinical correlates. Ann Intern Med. 1993;119:1198.CrossRefPubMed Boumpas DT, Chrousos GP, Wilder RL, Cupps TR, Balow JE. Glucocorticoid therapy for immune-mediated diseases: basic and clinical correlates. Ann Intern Med. 1993;119:1198.CrossRefPubMed
68.
go back to reference De Bosscher K, Haegeman G. Minireview: latest perspectives on anti-inflammatory actions of glucocorticoids. Mol Endocrinol. 2008;23:281–91.CrossRefPubMed De Bosscher K, Haegeman G. Minireview: latest perspectives on anti-inflammatory actions of glucocorticoids. Mol Endocrinol. 2008;23:281–91.CrossRefPubMed
69.
go back to reference Wang D, Müller N, McPherson KG, Reichardt HM. Glucocorticoids engage different signal transduction pathways to induce apoptosis in thymocytes and mature T cells. J. Immunol. 2006;176:1695–702.CrossRefPubMed Wang D, Müller N, McPherson KG, Reichardt HM. Glucocorticoids engage different signal transduction pathways to induce apoptosis in thymocytes and mature T cells. J. Immunol. 2006;176:1695–702.CrossRefPubMed
70.
go back to reference Franchimont D, Galon J, Gadina M, Visconti R, Zhou Y, Aringer M, et al. Inhibition of Th1 immune response by glucocorticoids: dexamethasone selectively inhibits IL-12-induced Stat4 phosphorylation in T lymphocytes. J. Immunol. 2000;164:1768–74.CrossRefPubMed Franchimont D, Galon J, Gadina M, Visconti R, Zhou Y, Aringer M, et al. Inhibition of Th1 immune response by glucocorticoids: dexamethasone selectively inhibits IL-12-induced Stat4 phosphorylation in T lymphocytes. J. Immunol. 2000;164:1768–74.CrossRefPubMed
Metadata
Title
Ouabain attenuates ovalbumin-induced airway inflammation
Authors
José Guilherme F. M. Galvão
Luiz Henrique Agra Cavalcante-Silva
Deyse Cristina M. Carvalho
Laércia Karla D. P. Ferreira
Talissa Mozzini Monteiro
Adriano Francisco Alves
Larissa Adilis M. P. Ferreira
Francisco Allysson A. F. Gadelha
Marcia Regina Piuvezam
Sandra Rodrigues-Mascarenhas
Publication date
01-12-2017
Publisher
Springer International Publishing
Published in
Inflammation Research / Issue 12/2017
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-017-1092-9

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