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This Article Full Text Full Text (PDF) All Versions of this Article: 295/5/L767    most recent 90351.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Lukacs, N. W. Articles by Bacon, K. B. Search for Related Content PubMed PubMed Citation Articles by Lukacs, N. W. Articles by Bacon, K. B.

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

Nicholas W. Lukacs,¹ Aaron A. Berlin,¹ Karin Franz-Bacon,² Roman áik,^3,4 L. James Sprague,³ Tai Wei Ly,² Gary Hardiman,^3,5 Stefen A. Boehme,² and Kevin B. Bacon²

¹Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan; ²Actimis Pharmaceuticals, Incorporated, ³Biomedical Genomics Microarray Facility (BIOGEM), School of Medicine, University of California, San Diego, ⁴Moore's Cancer Center, and ⁵Department of Medicine, University of California, La Jolla, California

Submitted 17 June 2008 ; accepted in final form 27 August 2008

Prostaglandin D₂, 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 PGD₂ 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 PGD₂-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.

prostaglandin D2; asthma

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