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http://purl.uniprot.org/citations/21059121http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/21059121http://www.w3.org/2000/01/rdf-schema#comment"

Background

Bronchial asthma is characterized by airway inflammation and reversible obstruction. Since the gold standard of therapy, a combination of anti-inflammatory corticosteroids and bronchodilatory β(2) agonists, has recently been discussed to be related to an increased mortality, there is a need for novel therapeutic pathways.

Objective

A new experimental concept that encompasses the vasoactive intestinal peptide/pituitary adenylate cyclase activating peptide (PACAP) family of receptors by demonstrating the anti-inflammatory effects of the PACAP receptor 1 (PAC1R) in a murine model of allergic asthma is described.

Methods

PAC1R expression was investigated in lung tissue and isolated dendritic cells (DCs) via real-time PCR. Ovalbumin (OVA)-induced asthma models were used in PAC1R-deficient mice and BALB/c mice treated with PAC1R agonist maxadilan (MAX). Bronchoalveolar lavages have been performed and investigated at the cellular and cytokine levels. Fluorescence staining of a frozen lung section has been performed to detect eosinophil granulocytes in lung tissue. Plasma IgE levels have been quantified via the ELISA technique. Lung function was determined using head-out body plethysmography or whole-body plethysmography.

Results

Increased PAC1R mRNA expression in lung tissue was present under inflammatory conditions. PAC1R expression was detected on DCs. In OVA-induced asthma models, which were applied to PAC1R-deficient mice (PAC1R(-/-)) and to BALB/c mice treated with the specific PAC1R agonist MAX, PAC1R deficiency resulted in inflammatory effects, while agonistic stimulation resulted in anti-inflammatory effects. No effects on lung function were detected both in the gene-depletion and in the pharmacologic studies. In summary, here, we demonstrate that anti-inflammatory effects can be achieved via PAC1R.

Conclusion

PAC1R agonists may represent a promising target for an anti-inflammatory therapy in airway diseases such as bronchial asthma."xsd:string
http://purl.uniprot.org/citations/21059121http://purl.org/dc/terms/identifier"doi:10.1111/j.1365-2222.2010.03636.x"xsd:string
http://purl.uniprot.org/citations/21059121http://purl.uniprot.org/core/author"Muller M."xsd:string
http://purl.uniprot.org/citations/21059121http://purl.uniprot.org/core/author"Braun A."xsd:string
http://purl.uniprot.org/citations/21059121http://purl.uniprot.org/core/author"Lerner E.A."xsd:string
http://purl.uniprot.org/citations/21059121http://purl.uniprot.org/core/author"Groneberg D.A."xsd:string
http://purl.uniprot.org/citations/21059121http://purl.uniprot.org/core/author"Welte T."xsd:string
http://purl.uniprot.org/citations/21059121http://purl.uniprot.org/core/author"Brabet P."xsd:string
http://purl.uniprot.org/citations/21059121http://purl.uniprot.org/core/author"Quarcoo D."xsd:string
http://purl.uniprot.org/citations/21059121http://purl.uniprot.org/core/author"Krug N."xsd:string
http://purl.uniprot.org/citations/21059121http://purl.uniprot.org/core/author"Hoymann H.G."xsd:string
http://purl.uniprot.org/citations/21059121http://purl.uniprot.org/core/author"Lauenstein H.D."xsd:string
http://purl.uniprot.org/citations/21059121http://purl.uniprot.org/core/author"Pilzner C."xsd:string
http://purl.uniprot.org/citations/21059121http://purl.uniprot.org/core/author"Nassimi M."xsd:string
http://purl.uniprot.org/citations/21059121http://purl.uniprot.org/core/author"Plappert L."xsd:string
http://purl.uniprot.org/citations/21059121http://purl.uniprot.org/core/author"Rochlitzer S."xsd:string
http://purl.uniprot.org/citations/21059121http://purl.uniprot.org/core/author"Schleh C."xsd:string
http://purl.uniprot.org/citations/21059121http://purl.uniprot.org/core/date"2011"xsd:gYear
http://purl.uniprot.org/citations/21059121http://purl.uniprot.org/core/name"Clin Exp Allergy"xsd:string
http://purl.uniprot.org/citations/21059121http://purl.uniprot.org/core/pages"592-601"xsd:string
http://purl.uniprot.org/citations/21059121http://purl.uniprot.org/core/title"Pituitary adenylate cyclase-activating peptide receptor 1 mediates anti-inflammatory effects in allergic airway inflammation in mice."xsd:string
http://purl.uniprot.org/citations/21059121http://purl.uniprot.org/core/volume"41"xsd:string
http://purl.uniprot.org/citations/21059121http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/21059121
http://purl.uniprot.org/citations/21059121http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/21059121
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