CRTH2 plays an essential role in the pathophysiology of Cry j 1-induced pollinosis in mice

Rie Nomiya, Mitsuhiro Okano, Tazuko Fujiwara, Megumi Maeda, Yoshinobu Kimura, Kosuke Kino, Minehiko Yokoyama, Hiroyuki Hirai, Kinya Nagata, Toshifumi Hara, Kazunori Nishizaki, Masataka Nakamura

Research output: Contribution to journalArticle

52 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)5680-5688
Number of pages9
JournalJournal of Immunology
Volume180
Issue number8
Publication statusPublished - Apr 15 2008

Fingerprint

Seasonal Allergic Rhinitis
Nose
Prostaglandin D2
Eosinophilia
Interleukin-4
Immunoglobulin E
Prostaglandins
Lymph Nodes
Cryptomeria
Formyl Peptide Receptor
Th2 Cells
Acute-Phase Reaction
Nasal Mucosa
Interleukin-5
Pollen
Allergy and Immunology
Allergens
Genes
Hypersensitivity
Messenger RNA

ASJC Scopus subject areas

  • Immunology

Cite this

Nomiya, R., Okano, M., Fujiwara, T., Maeda, M., Kimura, Y., Kino, K., ... Nakamura, M. (2008). CRTH2 plays an essential role in the pathophysiology of Cry j 1-induced pollinosis in mice. Journal of Immunology, 180(8), 5680-5688.

CRTH2 plays an essential role in the pathophysiology of Cry j 1-induced pollinosis in mice. / Nomiya, Rie; Okano, Mitsuhiro; Fujiwara, Tazuko; Maeda, Megumi; Kimura, Yoshinobu; Kino, Kosuke; Yokoyama, Minehiko; Hirai, Hiroyuki; Nagata, Kinya; Hara, Toshifumi; Nishizaki, Kazunori; Nakamura, Masataka.

In: Journal of Immunology, Vol. 180, No. 8, 15.04.2008, p. 5680-5688.

Research output: Contribution to journalArticle

Nomiya, R, Okano, M, Fujiwara, T, Maeda, M, Kimura, Y, Kino, K, Yokoyama, M, Hirai, H, Nagata, K, Hara, T, Nishizaki, K & Nakamura, M 2008, 'CRTH2 plays an essential role in the pathophysiology of Cry j 1-induced pollinosis in mice', Journal of Immunology, vol. 180, no. 8, pp. 5680-5688.
Nomiya, Rie ; Okano, Mitsuhiro ; Fujiwara, Tazuko ; Maeda, Megumi ; Kimura, Yoshinobu ; Kino, Kosuke ; Yokoyama, Minehiko ; Hirai, Hiroyuki ; Nagata, Kinya ; Hara, Toshifumi ; Nishizaki, Kazunori ; Nakamura, Masataka. / CRTH2 plays an essential role in the pathophysiology of Cry j 1-induced pollinosis in mice. In: Journal of Immunology. 2008 ; Vol. 180, No. 8. pp. 5680-5688.
@article{ff6184298cd34221bf8e7cbbfc9c026d,
title = "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 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.",
author = "Rie Nomiya and Mitsuhiro Okano and Tazuko Fujiwara and Megumi Maeda and Yoshinobu Kimura and Kosuke Kino and Minehiko Yokoyama and Hiroyuki Hirai and Kinya Nagata and Toshifumi Hara and Kazunori Nishizaki and Masataka Nakamura",
year = "2008",
month = "4",
day = "15",
language = "English",
volume = "180",
pages = "5680--5688",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "8",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=45949101464&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=45949101464&partnerID=8YFLogxK

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 -