A specific sphingosine kinase 1 inhibitor attenuates airway hyperresponsiveness and inflammation in a mast cell-dependent mouse model of allergic asthma

Autores
Price, Megan M.; Oskeritzian, Carole A.; Falanga, Yves T.; Harikumar, Kuzhuvelil B.; Allegood, Jeremy C.; Alvarez, Sergio Eduardo; Conrad, Daniel; Ryan, John J.; Milstien, Sheldon; Spiegel, Sarah
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Sphingosine-1-phosphate (S1P), which is produced by 2 sphingosine kinase (SphK) isoenzymes, SphK1 and SphK2, has been implicated in IgE-mediated mast cell responses. However, studies of allergic inflammation in isotype-specific SphK knockout mice have not clarified their contribution, and the role that S1P plays in vivo in a mast cells and IgE-dependent murine model of allergic asthma has not yet been examined. Objective: We used an isoenzyme-specific SphK1 inhibitor,SK1-I, to investigate the contributions of S1P and SphK1 to mast cell-dependent airway hyperresponsiveness (AHR) and airway inflammation in mice. Methods: Allergic airway inflammation and AHR were examined in a mast cell-dependent murine model of ovalbumin (OVA)-induced asthma. C57BL/6 mice received intranasal delivery of SK1-I before sensitization and challenge with OVA or only before challenge. Results: SK1-I inhibited antigen-dependent activation of human and murine mast cells and suppressed activation of nuclear factor-kB (NF-kB), a master transcription factor that regulates the expression of proinflammatory cytokines. SK1-I treatment of mice sensitized to OVA in the absence of adjuvant, in which mast cell-dependent allergic inflammation develops, significantly reduced OVA-induced AHR to methacholine; decreased numbers of eosinophils and levels of the cytokines IL-4, IL-5, IL-6, IL-13,IFN-g, and TNF-a and the chemokines eotaxin and CCL2 in bronchoalveolar lavage fluid; and decreased pulmonary inflammation, as well as activation of NF-kB in the lungs.
Fil: Price, Megan M.. Virginia Commonwealth University. School of Medicine. Department of Biochemistry and Molecular Biology; Estados Unidos
Fil: Oskeritzian, Carole A.. Virginia Commonwealth University. School of Medicine. Department of Biochemistry and Molecular Biology; Estados Unidos
Fil: Falanga, Yves T.. Virginia Commonwealth University. Department of Microbiology and Immunology; Estados Unidos
Fil: Harikumar, Kuzhuvelil B.. Virginia Commonwealth University. School of Medicine. Department of Biochemistry and Molecular Biology; Estados Unidos
Fil: Allegood, Jeremy C.. Virginia Commonwealth University. School of Medicine. Department of Biochemistry and Molecular Biology; Estados Unidos
Fil: Alvarez, Sergio Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Virginia Commonwealth University. School of Medicine. Department of Biochemistry and Molecular Biology; Estados Unidos
Fil: Conrad, Daniel. Virginia Commonwealth University. Department of Biology; Estados Unidos
Fil: Ryan, John J.. Virginia Commonwealth University. Department of Microbiology and Immunology; Estados Unidos
Fil: Milstien, Sheldon. Virginia Commonwealth University. School of Medicine. Department of Biochemistry and Molecular Biology; Estados Unidos
Fil: Spiegel, Sarah. Virginia Commonwealth University. School of Medicine. Department of Biochemistry and Molecular Biology; Estados Unidos
Materia
Sphingosine-1-Phosphate
Inflammation
Chemokines
Asthma
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/4364
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/4364
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A specific sphingosine kinase 1 inhibitor attenuates airway hyperresponsiveness and inflammation in a mast cell-dependent mouse model of allergic asthmaPrice, Megan M.Oskeritzian, Carole A.Falanga, Yves T.Harikumar, Kuzhuvelil B.Allegood, Jeremy C.Alvarez, Sergio EduardoConrad, DanielRyan, John J.Milstien, SheldonSpiegel, SarahSphingosine-1-PhosphateInflammationChemokinesAsthmahttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Background: Sphingosine-1-phosphate (S1P), which is produced by 2 sphingosine kinase (SphK) isoenzymes, SphK1 and SphK2, has been implicated in IgE-mediated mast cell responses. However, studies of allergic inflammation in isotype-specific SphK knockout mice have not clarified their contribution, and the role that S1P plays in vivo in a mast cells and IgE-dependent murine model of allergic asthma has not yet been examined. Objective: We used an isoenzyme-specific SphK1 inhibitor,SK1-I, to investigate the contributions of S1P and SphK1 to mast cell-dependent airway hyperresponsiveness (AHR) and airway inflammation in mice. Methods: Allergic airway inflammation and AHR were examined in a mast cell-dependent murine model of ovalbumin (OVA)-induced asthma. C57BL/6 mice received intranasal delivery of SK1-I before sensitization and challenge with OVA or only before challenge. Results: SK1-I inhibited antigen-dependent activation of human and murine mast cells and suppressed activation of nuclear factor-kB (NF-kB), a master transcription factor that regulates the expression of proinflammatory cytokines. SK1-I treatment of mice sensitized to OVA in the absence of adjuvant, in which mast cell-dependent allergic inflammation develops, significantly reduced OVA-induced AHR to methacholine; decreased numbers of eosinophils and levels of the cytokines IL-4, IL-5, IL-6, IL-13,IFN-g, and TNF-a and the chemokines eotaxin and CCL2 in bronchoalveolar lavage fluid; and decreased pulmonary inflammation, as well as activation of NF-kB in the lungs.Fil: Price, Megan M.. Virginia Commonwealth University. School of Medicine. Department of Biochemistry and Molecular Biology; Estados UnidosFil: Oskeritzian, Carole A.. Virginia Commonwealth University. School of Medicine. Department of Biochemistry and Molecular Biology; Estados UnidosFil: Falanga, Yves T.. Virginia Commonwealth University. Department of Microbiology and Immunology; Estados UnidosFil: Harikumar, Kuzhuvelil B.. Virginia Commonwealth University. School of Medicine. Department of Biochemistry and Molecular Biology; Estados UnidosFil: Allegood, Jeremy C.. Virginia Commonwealth University. School of Medicine. Department of Biochemistry and Molecular Biology; Estados UnidosFil: Alvarez, Sergio Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Virginia Commonwealth University. School of Medicine. Department of Biochemistry and Molecular Biology; Estados UnidosFil: Conrad, Daniel. Virginia Commonwealth University. Department of Biology; Estados UnidosFil: Ryan, John J.. Virginia Commonwealth University. Department of Microbiology and Immunology; Estados UnidosFil: Milstien, Sheldon. Virginia Commonwealth University. School of Medicine. Department of Biochemistry and Molecular Biology; Estados UnidosFil: Spiegel, Sarah. Virginia Commonwealth University. School of Medicine. Department of Biochemistry and Molecular Biology; Estados UnidosElsevier2013-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/4364Price, Megan M.; Oskeritzian, Carole A.; Falanga, Yves T.; Harikumar, Kuzhuvelil B.; Allegood, Jeremy C.; et al.; A specific sphingosine kinase 1 inhibitor attenuates airway hyperresponsiveness and inflammation in a mast cell-dependent mouse model of allergic asthma; Elsevier; Journal of Allergy and Clinical Immunology; 131; 2; 2-2013; 501-511.e10091-6749enginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S009167491201189Xinfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.jaci.2012.07.014info:eu-repo/semantics/altIdentifier/issn/0091-6749info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:07:53Zoai:ri.conicet.gov.ar:11336/4364instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 12:07:53.606CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A specific sphingosine kinase 1 inhibitor attenuates airway hyperresponsiveness and inflammation in a mast cell-dependent mouse model of allergic asthma
title A specific sphingosine kinase 1 inhibitor attenuates airway hyperresponsiveness and inflammation in a mast cell-dependent mouse model of allergic asthma
spellingShingle A specific sphingosine kinase 1 inhibitor attenuates airway hyperresponsiveness and inflammation in a mast cell-dependent mouse model of allergic asthma
Price, Megan M.
Sphingosine-1-Phosphate
Inflammation
Chemokines
Asthma
title_short A specific sphingosine kinase 1 inhibitor attenuates airway hyperresponsiveness and inflammation in a mast cell-dependent mouse model of allergic asthma
title_full A specific sphingosine kinase 1 inhibitor attenuates airway hyperresponsiveness and inflammation in a mast cell-dependent mouse model of allergic asthma
title_fullStr A specific sphingosine kinase 1 inhibitor attenuates airway hyperresponsiveness and inflammation in a mast cell-dependent mouse model of allergic asthma
title_full_unstemmed A specific sphingosine kinase 1 inhibitor attenuates airway hyperresponsiveness and inflammation in a mast cell-dependent mouse model of allergic asthma
title_sort A specific sphingosine kinase 1 inhibitor attenuates airway hyperresponsiveness and inflammation in a mast cell-dependent mouse model of allergic asthma
dc.creator.none.fl_str_mv Price, Megan M.
Oskeritzian, Carole A.
Falanga, Yves T.
Harikumar, Kuzhuvelil B.
Allegood, Jeremy C.
Alvarez, Sergio Eduardo
Conrad, Daniel
Ryan, John J.
Milstien, Sheldon
Spiegel, Sarah
author Price, Megan M.
author_facet Price, Megan M.
Oskeritzian, Carole A.
Falanga, Yves T.
Harikumar, Kuzhuvelil B.
Allegood, Jeremy C.
Alvarez, Sergio Eduardo
Conrad, Daniel
Ryan, John J.
Milstien, Sheldon
Spiegel, Sarah
author_role author
author2 Oskeritzian, Carole A.
Falanga, Yves T.
Harikumar, Kuzhuvelil B.
Allegood, Jeremy C.
Alvarez, Sergio Eduardo
Conrad, Daniel
Ryan, John J.
Milstien, Sheldon
Spiegel, Sarah
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Sphingosine-1-Phosphate
Inflammation
Chemokines
Asthma
topic Sphingosine-1-Phosphate
Inflammation
Chemokines
Asthma
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Background: Sphingosine-1-phosphate (S1P), which is produced by 2 sphingosine kinase (SphK) isoenzymes, SphK1 and SphK2, has been implicated in IgE-mediated mast cell responses. However, studies of allergic inflammation in isotype-specific SphK knockout mice have not clarified their contribution, and the role that S1P plays in vivo in a mast cells and IgE-dependent murine model of allergic asthma has not yet been examined. Objective: We used an isoenzyme-specific SphK1 inhibitor,SK1-I, to investigate the contributions of S1P and SphK1 to mast cell-dependent airway hyperresponsiveness (AHR) and airway inflammation in mice. Methods: Allergic airway inflammation and AHR were examined in a mast cell-dependent murine model of ovalbumin (OVA)-induced asthma. C57BL/6 mice received intranasal delivery of SK1-I before sensitization and challenge with OVA or only before challenge. Results: SK1-I inhibited antigen-dependent activation of human and murine mast cells and suppressed activation of nuclear factor-kB (NF-kB), a master transcription factor that regulates the expression of proinflammatory cytokines. SK1-I treatment of mice sensitized to OVA in the absence of adjuvant, in which mast cell-dependent allergic inflammation develops, significantly reduced OVA-induced AHR to methacholine; decreased numbers of eosinophils and levels of the cytokines IL-4, IL-5, IL-6, IL-13,IFN-g, and TNF-a and the chemokines eotaxin and CCL2 in bronchoalveolar lavage fluid; and decreased pulmonary inflammation, as well as activation of NF-kB in the lungs.
Fil: Price, Megan M.. Virginia Commonwealth University. School of Medicine. Department of Biochemistry and Molecular Biology; Estados Unidos
Fil: Oskeritzian, Carole A.. Virginia Commonwealth University. School of Medicine. Department of Biochemistry and Molecular Biology; Estados Unidos
Fil: Falanga, Yves T.. Virginia Commonwealth University. Department of Microbiology and Immunology; Estados Unidos
Fil: Harikumar, Kuzhuvelil B.. Virginia Commonwealth University. School of Medicine. Department of Biochemistry and Molecular Biology; Estados Unidos
Fil: Allegood, Jeremy C.. Virginia Commonwealth University. School of Medicine. Department of Biochemistry and Molecular Biology; Estados Unidos
Fil: Alvarez, Sergio Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Virginia Commonwealth University. School of Medicine. Department of Biochemistry and Molecular Biology; Estados Unidos
Fil: Conrad, Daniel. Virginia Commonwealth University. Department of Biology; Estados Unidos
Fil: Ryan, John J.. Virginia Commonwealth University. Department of Microbiology and Immunology; Estados Unidos
Fil: Milstien, Sheldon. Virginia Commonwealth University. School of Medicine. Department of Biochemistry and Molecular Biology; Estados Unidos
Fil: Spiegel, Sarah. Virginia Commonwealth University. School of Medicine. Department of Biochemistry and Molecular Biology; Estados Unidos
description Background: Sphingosine-1-phosphate (S1P), which is produced by 2 sphingosine kinase (SphK) isoenzymes, SphK1 and SphK2, has been implicated in IgE-mediated mast cell responses. However, studies of allergic inflammation in isotype-specific SphK knockout mice have not clarified their contribution, and the role that S1P plays in vivo in a mast cells and IgE-dependent murine model of allergic asthma has not yet been examined. Objective: We used an isoenzyme-specific SphK1 inhibitor,SK1-I, to investigate the contributions of S1P and SphK1 to mast cell-dependent airway hyperresponsiveness (AHR) and airway inflammation in mice. Methods: Allergic airway inflammation and AHR were examined in a mast cell-dependent murine model of ovalbumin (OVA)-induced asthma. C57BL/6 mice received intranasal delivery of SK1-I before sensitization and challenge with OVA or only before challenge. Results: SK1-I inhibited antigen-dependent activation of human and murine mast cells and suppressed activation of nuclear factor-kB (NF-kB), a master transcription factor that regulates the expression of proinflammatory cytokines. SK1-I treatment of mice sensitized to OVA in the absence of adjuvant, in which mast cell-dependent allergic inflammation develops, significantly reduced OVA-induced AHR to methacholine; decreased numbers of eosinophils and levels of the cytokines IL-4, IL-5, IL-6, IL-13,IFN-g, and TNF-a and the chemokines eotaxin and CCL2 in bronchoalveolar lavage fluid; and decreased pulmonary inflammation, as well as activation of NF-kB in the lungs.
publishDate 2013
dc.date.none.fl_str_mv 2013-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/4364
Price, Megan M.; Oskeritzian, Carole A.; Falanga, Yves T.; Harikumar, Kuzhuvelil B.; Allegood, Jeremy C.; et al.; A specific sphingosine kinase 1 inhibitor attenuates airway hyperresponsiveness and inflammation in a mast cell-dependent mouse model of allergic asthma; Elsevier; Journal of Allergy and Clinical Immunology; 131; 2; 2-2013; 501-511.e1
0091-6749
url http://hdl.handle.net/11336/4364
identifier_str_mv Price, Megan M.; Oskeritzian, Carole A.; Falanga, Yves T.; Harikumar, Kuzhuvelil B.; Allegood, Jeremy C.; et al.; A specific sphingosine kinase 1 inhibitor attenuates airway hyperresponsiveness and inflammation in a mast cell-dependent mouse model of allergic asthma; Elsevier; Journal of Allergy and Clinical Immunology; 131; 2; 2-2013; 501-511.e1
0091-6749
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S009167491201189X
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.jaci.2012.07.014
info:eu-repo/semantics/altIdentifier/issn/0091-6749
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.982451

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