Results

RDF/XMLNTriplesTurtleShow queryShare ▶
SubjectPredicateObject
http://purl.uniprot.org/citations/21047676http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/21047676http://www.w3.org/2000/01/rdf-schema#comment"

Background

Cyclic AMP (cAMP) signaling modulates functions of inflammatory cells involved in the pathogenesis of asthma, and type 4 cAMP-specific phosphodiesterases (PDE4s) are essential components of this pathway. Induction of the PDE4 isoform PDE4B is necessary for Toll-like receptor signaling in monocytes and macrophages and is associated with T cell receptor/CD3 in T cells; however, its exact physiological function in the development of allergic asthma remains undefined.

Objectives

We investigated the role of PDE4B in the development of allergen-induced airway hyperresponsiveness (AHR) and T(H)2-driven inflammatory responses.

Methods

Wild-type and PDE4B(-/-) mice were sensitized and challenged with ovalbumin and AHR measured in response to inhaled methacholine. Airway inflammation was characterized by analyzing leukocyte infiltration and cytokine accumulation in the airways. Ovalbumin-stimulated cell proliferation and T(H)2 cytokine production were determined in cultured bronchial lymph node cells.

Results

Mice deficient in PDE4B do not develop AHR. This protective effect was associated with a significant decrease in eosinophils recruitment to the lungs and decreased T(H)2 cytokine levels in the bronchoalveolar lavage fluid. Defects in T-cell replication, T(H)2 cytokine production, and dendritic cell migration were evident in cells from the airway-draining lymph nodes. Conversely, accumulation of the T(H)1 cytokine IFN-γ was not affected in PDE4B(-/-) mice. Ablation of the orthologous PDE4 gene PDE4A has no impact on airway inflammation.

Conclusion

By relieving a cAMP-negative constraint, PDE4B plays an essential role in T(H)2-cell activation and dendritic cell recruitment during airway inflammation. These findings provide proof of concept that PDE4 inhibitors with PDE4B selectivity may have efficacy in asthma treatment."xsd:string
http://purl.uniprot.org/citations/21047676http://purl.org/dc/terms/identifier"doi:10.1016/j.jaci.2010.08.014"xsd:string
http://purl.uniprot.org/citations/21047676http://purl.uniprot.org/core/author"Wang D."xsd:string
http://purl.uniprot.org/citations/21047676http://purl.uniprot.org/core/author"Hou C."xsd:string
http://purl.uniprot.org/citations/21047676http://purl.uniprot.org/core/author"Bruss M."xsd:string
http://purl.uniprot.org/citations/21047676http://purl.uniprot.org/core/author"Conti M."xsd:string
http://purl.uniprot.org/citations/21047676http://purl.uniprot.org/core/author"Nakae S."xsd:string
http://purl.uniprot.org/citations/21047676http://purl.uniprot.org/core/author"Goya S."xsd:string
http://purl.uniprot.org/citations/21047676http://purl.uniprot.org/core/author"Umetsu D."xsd:string
http://purl.uniprot.org/citations/21047676http://purl.uniprot.org/core/author"Jin S.L."xsd:string
http://purl.uniprot.org/citations/21047676http://purl.uniprot.org/core/date"2010"xsd:gYear
http://purl.uniprot.org/citations/21047676http://purl.uniprot.org/core/name"J Allergy Clin Immunol"xsd:string
http://purl.uniprot.org/citations/21047676http://purl.uniprot.org/core/pages"1252-9.e12"xsd:string
http://purl.uniprot.org/citations/21047676http://purl.uniprot.org/core/title"Phosphodiesterase 4B is essential for T(H)2-cell function and development of airway hyperresponsiveness in allergic asthma."xsd:string
http://purl.uniprot.org/citations/21047676http://purl.uniprot.org/core/volume"126"xsd:string
http://purl.uniprot.org/citations/21047676http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/21047676
http://purl.uniprot.org/citations/21047676http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/21047676
http://purl.uniprot.org/uniprot/#_B2RTL2-mappedCitation-21047676http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21047676
http://purl.uniprot.org/uniprot/#_B1AWC8-mappedCitation-21047676http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21047676
http://purl.uniprot.org/uniprot/#_B1AWC9-mappedCitation-21047676http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21047676
http://purl.uniprot.org/uniprot/#_B1AWD0-mappedCitation-21047676http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21047676
http://purl.uniprot.org/uniprot/#_B1AWD1-mappedCitation-21047676http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21047676
http://purl.uniprot.org/uniprot/#_G3UWT3-mappedCitation-21047676http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21047676
http://purl.uniprot.org/uniprot/#_C9K100-mappedCitation-21047676http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21047676
▶