CRTH2 plays an essential role in the pathophysiology of Cry j 1-induced pollinosis in mice.
PGD(2) is the major prostanoid produced during the acute phase of allergic reactions. Two PGD(2) 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 PGD(2)-CRTH2 interaction is elevated following sensitization and plays a proinflammatory role in the pathophysiology of allergic rhinitis, especially pollinosis in mice.
Nomiya
Rie
R
Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Okano
Mitsuhiro
M
Fujiwara
Tazuko
T
Maeda
Megumi
M
Kimura
Yoshinobu
Y
Kino
Kosuke
K
Yokoyama
Minehiko
M
Hirai
Hiroyuki
H
Nagata
Kinya
K
Hara
Toshifumi
T
Nishizaki
Kazunori
K
Nakamura
Masataka
M
D000485:Allergens / Q000276:immunology*; D000818:Animals; D052179:Antigens, Plant; D002227:Carbazoles / Q000494:pharmacology; D032485:Cryptomeria / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology; D007136:Immunoglobulins / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D009297:Nasal Mucosa / Q000276:immunology / Q000378:metabolism; D009300:Nasal Septum / Q000276:immunology; D010940:Plant Proteins / Q000276:immunology*; D011058:Pollen / Q000276:immunology; D015230:Prostaglandin D2 / Q000378:metabolism; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000502:physiology*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors / Q000502:physiology*; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D013449:Sulfonamides / Q000494:pharmacology; D018418:Th2 Cells / Q000276:immunology
D000485:Allergens; D052179:Antigens, Plant; D002227:Carbazoles; C065290:Cry j I protein, Cryptomeria japonica; D016207:Cytokines; D007136:Immunoglobulins; D010940:Plant Proteins; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D013449:Sulfonamides; C063119:ramatroban; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor