RGD Reference Report - CRTH2 antagonism significantly ameliorates airway hyperreactivity and downregulates inflammation-induced genes in a mouse model of airway inflammation. - Rat Genome Database

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CRTH2 antagonism significantly ameliorates airway hyperreactivity and downregulates inflammation-induced genes in a mouse model of airway inflammation.

Authors: Lukacs, NW  Berlin, AA  Franz-Bacon, K  Sasik, R  Sprague, LJ  Ly, TW  Hardiman, G  Boehme, SA  Bacon, KB 
Citation: Lukacs NW, etal., Am J Physiol Lung Cell Mol Physiol. 2008 Nov;295(5):L767-79. Epub 2008 Aug 29.
RGD ID: 5135018
Pubmed: PMID:18757520   (View Abstract at PubMed)
PMCID: PMC2584886   (View Article at PubMed Central)
DOI: DOI:10.1152/ajplung.90351.2008   (Journal Full-text)

Prostaglandin D(2), the ligand for the G protein-coupled receptors DP1 and CRTH2, has been implicated in the pathogenesis of the allergic response in diseases such as asthma, rhinitis, and atopic dermatitis. This prostanoid also fulfills a number of physiological, anti-inflammatory roles through its receptor DP1. We investigated the role of PGD(2) and CRTH2 in allergic pulmonary inflammation by using a highly potent and specific antagonist of CRTH2. Administration of this antagonist ameliorated inflammation caused by either acute or subchronic sensitization using the cockroach egg antigen. Gene expression and ELISA analysis revealed that there was reduced proinflammatory cytokine mRNA or protein produced, as well as a wide array of genes associated with the Th2-type proinflammatory response. Importantly, the CRTH2 antagonist reduced antigen-specific IgE, IgG1, and IgG2a antibody levels as well as decreased mucus deposition and leukocyte infiltration in the large airways. Collectively, these findings suggest that the PGD(2)-CRTH2 activation axis has a pivotal role in mediating the inflammation and the underlying immune response in a T cell-driven model of allergic airway inflammation.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
asthma  ISOPtgdr2 (Mus musculus)5135018; 5135018 RGD 
asthma  IMP 5135018 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ptgdr2  (prostaglandin D2 receptor 2)

Genes (Mus musculus)
Ptgdr2  (prostaglandin D2 receptor 2)

Genes (Homo sapiens)
PTGDR2  (prostaglandin D2 receptor 2)


Additional Information