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dc.contributor.author
Price, Megan M.
dc.contributor.author
Oskeritzian, Carole A.
dc.contributor.author
Falanga, Yves T.
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Harikumar, Kuzhuvelil B.
dc.contributor.author
Allegood, Jeremy C.
dc.contributor.author
Alvarez, Sergio Eduardo
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dc.contributor.author
Conrad, Daniel
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Ryan, John J.
dc.contributor.author
Milstien, Sheldon
dc.contributor.author
Spiegel, Sarah
dc.date.available
2016-02-22T19:44:51Z
dc.date.issued
2013-02
dc.identifier.citation
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
dc.identifier.issn
0091-6749
dc.identifier.uri
http://hdl.handle.net/11336/4364
dc.description.abstract
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Elsevier
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Sphingosine-1-Phosphate
dc.subject
Inflammation
dc.subject
Chemokines
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Asthma
dc.subject.classification
Biología Celular, Microbiología
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dc.subject.classification
Ciencias Biológicas
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dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
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dc.title
A specific sphingosine kinase 1 inhibitor attenuates airway hyperresponsiveness and inflammation in a mast cell-dependent mouse model of allergic asthma
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2016-03-30 10:35:44.97925-03
dc.journal.volume
131
dc.journal.number
2
dc.journal.pagination
501-511.e1
dc.journal.pais
Países Bajos
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dc.journal.ciudad
Amsterdam
dc.description.fil
Fil: Price, Megan M.. Virginia Commonwealth University. School of Medicine. Department of Biochemistry and Molecular Biology; Estados Unidos
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Fil: Oskeritzian, Carole A.. Virginia Commonwealth University. School of Medicine. Department of Biochemistry and Molecular Biology; Estados Unidos
dc.description.fil
Fil: Falanga, Yves T.. Virginia Commonwealth University. Department of Microbiology and Immunology; Estados Unidos
dc.description.fil
Fil: Harikumar, Kuzhuvelil B.. Virginia Commonwealth University. School of Medicine. Department of Biochemistry and Molecular Biology; Estados Unidos
dc.description.fil
Fil: Allegood, Jeremy C.. Virginia Commonwealth University. School of Medicine. Department of Biochemistry and Molecular Biology; Estados Unidos
dc.description.fil
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
dc.description.fil
Fil: Conrad, Daniel. Virginia Commonwealth University. Department of Biology; Estados Unidos
dc.description.fil
Fil: Ryan, John J.. Virginia Commonwealth University. Department of Microbiology and Immunology; Estados Unidos
dc.description.fil
Fil: Milstien, Sheldon. Virginia Commonwealth University. School of Medicine. Department of Biochemistry and Molecular Biology; Estados Unidos
dc.description.fil
Fil: Spiegel, Sarah. Virginia Commonwealth University. School of Medicine. Department of Biochemistry and Molecular Biology; Estados Unidos
dc.journal.title
Journal of Allergy and Clinical Immunology
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S009167491201189X
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.jaci.2012.07.014
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/issn/0091-6749
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