CRTH2 Plays an Essential Role in the Pathophysiology of Cry j 1-Induced Pollinosis in Mice

Abstract

PGD2 is the major prostanoid produced during the acute phase of allergic reactions. Two PGD2 receptors have been isolated, DP and CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells), but whether they participate in the pathophysiology of allergic diseases remains unclear. We investigated the role of CRTH2 in the initiation of allergic rhinitis in mice. First, we developed a novel murine model of pollinosis, a type of seasonal allergic rhinitis. Additionally, pathophysiological differences in the pollinosis were compared between wild-type and CRTH2 gene-deficient mice. An effect of treatment with ramatroban, a CRTH2/T-prostanoid receptor dual antagonist, was also determined. Repeated intranasal sensitization with Cry j 1, the major allergen of Cryptomeria japonica pollen, in the absence of adjuvants significantly exacerbated nasal hyperresponsive symptoms, Cry j 1-specific IgE and IgG1 production, nasal eosinophilia, and Cry j 1-induced in vitro production of IL-4 and IL-5 by submandibular lymph node cells. Additionally, CRTH2 mRNA in nasal mucosa was significantly elevated in Cry j 1-sensitized mice. Following repeated intranasal sensitization with Cry j 1, CRTH2 gene-deficient mice had significantly weaker Cry j 1-specific IgE/IgG1 production, nasal eosinophilia, and IL-4 production by submandibular lymph node cells than did wild-type mice. Similar results were found in mice treated with ramatroban. These results suggest that the PGD2-CRTH2 interaction is elevated following sensitization and plays a proinflammatory role in the pathophysiology of allergic rhinitis, especially pollinosis in mice.

DP2 (CRTh2) Antagonism Reduces Ocular Inflammation Induced by Allergen Challenge and Respiratory Syncytial Virus

“…The role for PGD 2 and DP2 in allergic airway and allergic cutaneous disease has been extensively explored [19,28,29,30,31,32]. However, to our knowledge, these data are the first to report efficacy of a selective DP2 antagonist in in vivo ocular models of allergic conjunctivitis and RSV inflammation.…”

α-Melanocyte-Stimulating Hormone Plays an Important Role in the Onset of Pollinosis in a Pollen Allergy Mouse Model

“…These experiments employed the methods of Nomiya et al [12]. The mice were sensitized with 10 µg of Cry j I (Hayashibara, Okayama, Japan) mixed with 4 mg of aluminum hydroxide gel (Sigma, St Louis, Mo., USA) by subcutaneous injection, which was administered 3 times every other day.…”

“…This study examined sneezing and tracheal inflammation associated with pollinosis using the pollen allergy model of Nomiya et al [12]. …”

“…Two major allergens, Cry j I and Cry j II, have been isolated from C. japonica pollen [8,9], and an effective animal model using Cry j I has been developed [5,6,7,10,11,12]. Antigen-induced nasal symptoms, late-phase nasal eosinophilia, and serum levels of antigen-specific IgE antibody were evaluated in an ovalbumin-sensitized BALB/c mouse model of allergic rhinitis [6,12,13].…”

“…Antigen-induced nasal symptoms, late-phase nasal eosinophilia, and serum levels of antigen-specific IgE antibody were evaluated in an ovalbumin-sensitized BALB/c mouse model of allergic rhinitis [6,12,13]. …”