title: CRTH2 antagonism significantly ameliorates airway hyperreactivity and downregulates inflammation-induced genes in a mouse model of airway inflammation.
abstract: 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.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Lukacs
authors.forename: Aaron A
authors.initials: AA
authors.lastname: Berlin
authors.forename: Karin
authors.initials: K
authors.lastname: Franz-Bacon
authors.forename: Roman
authors.initials: R
authors.lastname: Sásik
authors.forename: L James
authors.initials: LJ
authors.lastname: Sprague
authors.forename: Tai Wei
authors.initials: TW
authors.lastname: Ly
authors.forename: Gary
authors.initials: G
authors.lastname: Hardiman
authors.forename: Stefen A
authors.initials: SA
authors.lastname: Boehme
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Bacon