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Antigen-induced airway hyperresponsiveness and obstruction is related to caveolin-1 expression in airway smooth muscle in a guinea pig asthma model

BACKGROUND: Caveolin-1 is a fundamental signalling scaffold protein involved in contraction; however, the role of caveolin-1 in airway responsiveness remains unclear. We evaluated the relationship between caveolin-1 expression in airway smooth muscle (ASM) and antigen-induced airway responsiveness a...

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Autores principales: Álvarez-Santos, Mayra, Ramos-Ramírez, Patricia, Gutiérrez-Aguilar, Fernando, Sánchez-Hernández, Sandra, Lascurain, Ricardo, Olmos-Zuñiga, Raúl, Jasso-Victoria, Rogelio, Bobadilla, Norma A, Bazan-Perkins, Blanca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4431535/
https://www.ncbi.nlm.nih.gov/pubmed/25977751
http://dx.doi.org/10.1186/s13601-015-0058-7
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author Álvarez-Santos, Mayra
Ramos-Ramírez, Patricia
Gutiérrez-Aguilar, Fernando
Sánchez-Hernández, Sandra
Lascurain, Ricardo
Olmos-Zuñiga, Raúl
Jasso-Victoria, Rogelio
Bobadilla, Norma A
Bazan-Perkins, Blanca
author_facet Álvarez-Santos, Mayra
Ramos-Ramírez, Patricia
Gutiérrez-Aguilar, Fernando
Sánchez-Hernández, Sandra
Lascurain, Ricardo
Olmos-Zuñiga, Raúl
Jasso-Victoria, Rogelio
Bobadilla, Norma A
Bazan-Perkins, Blanca
author_sort Álvarez-Santos, Mayra
collection PubMed
description BACKGROUND: Caveolin-1 is a fundamental signalling scaffold protein involved in contraction; however, the role of caveolin-1 in airway responsiveness remains unclear. We evaluated the relationship between caveolin-1 expression in airway smooth muscle (ASM) and antigen-induced airway responsiveness and obstruction in a guinea pig asthma model. METHODS: Airway obstruction in sensitised guinea pigs, induced by antigenic (ovalbumin) challenges administered every 10 days, was measured. Antigen-induced responsiveness to histamine and the expression of caveolin-1 and cavin 1, 2 and 3 were evaluated at the third ovalbumin challenge. The control group received saline solution instead of ovalbumin. RESULTS: After the first challenge, antigen exposure induced a transient airway obstruction and airway hyperresponsiveness, high levels of IL-4 and IL-5 in lung and airway globet cells proliferation at the third antigenic challenge. Caveolin-1 mRNA levels in total lung decreased in the experimental group compared with controls. Flow cytometric analysis of ASM from the experimental group showed a high number of cells expressing caveolin-1 compared with controls. This increase was confirmed by western blot. Airway obstruction and hyperresponsiveness correlated with the degree of increased caveolin-1 expression in ASM cells (P < 0.05; r = 0.69 and −0.52, respectively). The expression of cavins 1, 2 and 3 in ASM also increased in the experimental group compared to controls. Immunohistochemical findings reveal that differences in ASM caveolin-1 were not evident between groups. Nevertheless, a marked decrease in caveolin-1 and caspase 3 was observed in the pulmonary vascular smooth muscle of asthma model compared with controls. Histological analysis did not reveal differences in smooth muscles mass or subepithelial fibrosis levels in airways between groups. However, an enlargement of smooth muscle mass was observed in the pulmonary microvessels of experimental animals. This enlargement did not induce changes in pulmonary or systemic arterial pressures. CONCLUSIONS: Our data suggest that caveolin-1 expression in ASM has a crucial role in the development of antigen-induced airway obstruction and hyperresponsiveness in a guinea pig asthma model. In addition, the asthma model in guinea pigs appears to induce a contractile smooth muscle phenotype in the airways and a proliferative smooth muscle phenotype in pulmonary vessels.
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spelling pubmed-44315352015-05-15 Antigen-induced airway hyperresponsiveness and obstruction is related to caveolin-1 expression in airway smooth muscle in a guinea pig asthma model Álvarez-Santos, Mayra Ramos-Ramírez, Patricia Gutiérrez-Aguilar, Fernando Sánchez-Hernández, Sandra Lascurain, Ricardo Olmos-Zuñiga, Raúl Jasso-Victoria, Rogelio Bobadilla, Norma A Bazan-Perkins, Blanca Clin Transl Allergy Research BACKGROUND: Caveolin-1 is a fundamental signalling scaffold protein involved in contraction; however, the role of caveolin-1 in airway responsiveness remains unclear. We evaluated the relationship between caveolin-1 expression in airway smooth muscle (ASM) and antigen-induced airway responsiveness and obstruction in a guinea pig asthma model. METHODS: Airway obstruction in sensitised guinea pigs, induced by antigenic (ovalbumin) challenges administered every 10 days, was measured. Antigen-induced responsiveness to histamine and the expression of caveolin-1 and cavin 1, 2 and 3 were evaluated at the third ovalbumin challenge. The control group received saline solution instead of ovalbumin. RESULTS: After the first challenge, antigen exposure induced a transient airway obstruction and airway hyperresponsiveness, high levels of IL-4 and IL-5 in lung and airway globet cells proliferation at the third antigenic challenge. Caveolin-1 mRNA levels in total lung decreased in the experimental group compared with controls. Flow cytometric analysis of ASM from the experimental group showed a high number of cells expressing caveolin-1 compared with controls. This increase was confirmed by western blot. Airway obstruction and hyperresponsiveness correlated with the degree of increased caveolin-1 expression in ASM cells (P < 0.05; r = 0.69 and −0.52, respectively). The expression of cavins 1, 2 and 3 in ASM also increased in the experimental group compared to controls. Immunohistochemical findings reveal that differences in ASM caveolin-1 were not evident between groups. Nevertheless, a marked decrease in caveolin-1 and caspase 3 was observed in the pulmonary vascular smooth muscle of asthma model compared with controls. Histological analysis did not reveal differences in smooth muscles mass or subepithelial fibrosis levels in airways between groups. However, an enlargement of smooth muscle mass was observed in the pulmonary microvessels of experimental animals. This enlargement did not induce changes in pulmonary or systemic arterial pressures. CONCLUSIONS: Our data suggest that caveolin-1 expression in ASM has a crucial role in the development of antigen-induced airway obstruction and hyperresponsiveness in a guinea pig asthma model. In addition, the asthma model in guinea pigs appears to induce a contractile smooth muscle phenotype in the airways and a proliferative smooth muscle phenotype in pulmonary vessels. BioMed Central 2015-03-26 /pmc/articles/PMC4431535/ /pubmed/25977751 http://dx.doi.org/10.1186/s13601-015-0058-7 Text en © Alvarez-Santos et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Álvarez-Santos, Mayra
Ramos-Ramírez, Patricia
Gutiérrez-Aguilar, Fernando
Sánchez-Hernández, Sandra
Lascurain, Ricardo
Olmos-Zuñiga, Raúl
Jasso-Victoria, Rogelio
Bobadilla, Norma A
Bazan-Perkins, Blanca
Antigen-induced airway hyperresponsiveness and obstruction is related to caveolin-1 expression in airway smooth muscle in a guinea pig asthma model
title Antigen-induced airway hyperresponsiveness and obstruction is related to caveolin-1 expression in airway smooth muscle in a guinea pig asthma model
title_full Antigen-induced airway hyperresponsiveness and obstruction is related to caveolin-1 expression in airway smooth muscle in a guinea pig asthma model
title_fullStr Antigen-induced airway hyperresponsiveness and obstruction is related to caveolin-1 expression in airway smooth muscle in a guinea pig asthma model
title_full_unstemmed Antigen-induced airway hyperresponsiveness and obstruction is related to caveolin-1 expression in airway smooth muscle in a guinea pig asthma model
title_short Antigen-induced airway hyperresponsiveness and obstruction is related to caveolin-1 expression in airway smooth muscle in a guinea pig asthma model
title_sort antigen-induced airway hyperresponsiveness and obstruction is related to caveolin-1 expression in airway smooth muscle in a guinea pig asthma model
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4431535/
https://www.ncbi.nlm.nih.gov/pubmed/25977751
http://dx.doi.org/10.1186/s13601-015-0058-7
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