TY - JOUR
T1 - CRTH2 plays an essential role in the pathophysiology of Cry j 1-induced pollinosis in mice
AU - Nomiya, Rie
AU - Okano, Mitsuhiro
AU - Fujiwara, Tazuko
AU - Maeda, Megumi
AU - Kimura, Yoshinobu
AU - Kino, Kosuke
AU - Yokoyama, Minehiko
AU - Hirai, Hiroyuki
AU - Nagata, Kinya
AU - Hara, Toshifumi
AU - Nishizaki, Kazunori
AU - Nakamura, Masataka
PY - 2008/4/15
Y1 - 2008/4/15
N2 - 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 IgGl 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/IgGl 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. The Journal of Immunology, 2008, 180: 5680-5688.
AB - 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 IgGl 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/IgGl 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. The Journal of Immunology, 2008, 180: 5680-5688.
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U2 - 10.4049/jimmunol.180.8.5680
DO - 10.4049/jimmunol.180.8.5680
M3 - Article
C2 - 18390753
AN - SCOPUS:45949101464
VL - 180
SP - 5680
EP - 5688
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 8
ER -