Cyclooxygenase-2/prostaglandin D2/CRTH2 pathway mediates double-stranded RNA-induced enhancement of allergic airway inflammation

Yoshiki Shiraishi, Koichiro Asano, Kyoko Niimi, Koichi Fukunaga, Misa Wakaki, Junko Kagyo, Takahisa Takihara, Soichiro Ueda, Takeshi Nakajima, Tsuyoshi Oguma, Yusuke Suzuki, Tetsuya Shiomi, Koichi Sayama, Shizuko Kagawa, Eiji Ikeda, Hiroyuki Hirai, Kinya Nagata, Masataka Nakamura, Taku Miyasho, Akitoshi Ishizaka

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Respiratory RNA viruses responsible for the common cold often worsen airway inflammation and bronchial responsiveness, two characteristic features of human asthma. We studied the effects of dsRNA, a nucleotide synthesized during viral replication, on airway inflammation and bronchial hyperresponsiveness in murine models of asthma. Intratracheal instillation of poly I:C, a synthetic dsRNA, increased the airway eosinophilia and enhanced bronchial hyperresponsiveness to methacholine in OVA-sensitized, exposed rats. These changes were associated with induction of cyclooxygenase-2 (COX-2) expression and COX-2-dependent PGD 2 synthesis in the lungs, particularly in alveolar macrophages. The direct intratracheal instillation of PGD2 enhanced the eosinophilic inflammation in OVA-exposed animals, whereas pretreatment with a dual antagonist against the PGD2 receptor-(CRTH2) and the thromboxane A2 receptor, but not with a thromboxane A2 receptor-specific antagonist, nearly completely eliminated the dsRNA-induced worsening of airway inflammation and bronchial hyperresponsiveness. CRTH2-deficient mice had the same degree of allergen-induced airway eosinophilia as wild-type mice, but they did not exhibit a dsRNA-induced increase in eosinophil accumulation. Our data demonstrate that COX-2-dependent production of PGD2 followed by eosinophil recruitment into the airways via a CRTH2 receptor are the major pathogenetic factors responsible for the dsRNA-induced enhancement of airway inflammation and responsiveness.

Original languageEnglish
Pages (from-to)541-549
Number of pages9
JournalJournal of Immunology
Volume180
Issue number1
Publication statusPublished - 2008 Jan 1

Fingerprint

Prostaglandin D2
Double-Stranded RNA
Cyclooxygenase 2
Inflammation
Prostaglandin H2 Receptors Thromboxane A2
Eosinophilia
Eosinophils
Asthma
Prostaglandins D
Poly I-C
Common Cold
Methacholine Chloride
RNA Viruses
Alveolar Macrophages
Allergens
Nucleotides
Lung

ASJC Scopus subject areas

  • Immunology

Cite this

Cyclooxygenase-2/prostaglandin D2/CRTH2 pathway mediates double-stranded RNA-induced enhancement of allergic airway inflammation. / Shiraishi, Yoshiki; Asano, Koichiro; Niimi, Kyoko; Fukunaga, Koichi; Wakaki, Misa; Kagyo, Junko; Takihara, Takahisa; Ueda, Soichiro; Nakajima, Takeshi; Oguma, Tsuyoshi; Suzuki, Yusuke; Shiomi, Tetsuya; Sayama, Koichi; Kagawa, Shizuko; Ikeda, Eiji; Hirai, Hiroyuki; Nagata, Kinya; Nakamura, Masataka; Miyasho, Taku; Ishizaka, Akitoshi.

In: Journal of Immunology, Vol. 180, No. 1, 01.01.2008, p. 541-549.

Research output: Contribution to journalArticle

Shiraishi, Y, Asano, K, Niimi, K, Fukunaga, K, Wakaki, M, Kagyo, J, Takihara, T, Ueda, S, Nakajima, T, Oguma, T, Suzuki, Y, Shiomi, T, Sayama, K, Kagawa, S, Ikeda, E, Hirai, H, Nagata, K, Nakamura, M, Miyasho, T & Ishizaka, A 2008, 'Cyclooxygenase-2/prostaglandin D2/CRTH2 pathway mediates double-stranded RNA-induced enhancement of allergic airway inflammation', Journal of Immunology, vol. 180, no. 1, pp. 541-549.
Shiraishi, Yoshiki ; Asano, Koichiro ; Niimi, Kyoko ; Fukunaga, Koichi ; Wakaki, Misa ; Kagyo, Junko ; Takihara, Takahisa ; Ueda, Soichiro ; Nakajima, Takeshi ; Oguma, Tsuyoshi ; Suzuki, Yusuke ; Shiomi, Tetsuya ; Sayama, Koichi ; Kagawa, Shizuko ; Ikeda, Eiji ; Hirai, Hiroyuki ; Nagata, Kinya ; Nakamura, Masataka ; Miyasho, Taku ; Ishizaka, Akitoshi. / Cyclooxygenase-2/prostaglandin D2/CRTH2 pathway mediates double-stranded RNA-induced enhancement of allergic airway inflammation. In: Journal of Immunology. 2008 ; Vol. 180, No. 1. pp. 541-549.
@article{240d5cb7bb9d43e6b6d561c7a31af8ed,
title = "Cyclooxygenase-2/prostaglandin D2/CRTH2 pathway mediates double-stranded RNA-induced enhancement of allergic airway inflammation",
abstract = "Respiratory RNA viruses responsible for the common cold often worsen airway inflammation and bronchial responsiveness, two characteristic features of human asthma. We studied the effects of dsRNA, a nucleotide synthesized during viral replication, on airway inflammation and bronchial hyperresponsiveness in murine models of asthma. Intratracheal instillation of poly I:C, a synthetic dsRNA, increased the airway eosinophilia and enhanced bronchial hyperresponsiveness to methacholine in OVA-sensitized, exposed rats. These changes were associated with induction of cyclooxygenase-2 (COX-2) expression and COX-2-dependent PGD 2 synthesis in the lungs, particularly in alveolar macrophages. The direct intratracheal instillation of PGD2 enhanced the eosinophilic inflammation in OVA-exposed animals, whereas pretreatment with a dual antagonist against the PGD2 receptor-(CRTH2) and the thromboxane A2 receptor, but not with a thromboxane A2 receptor-specific antagonist, nearly completely eliminated the dsRNA-induced worsening of airway inflammation and bronchial hyperresponsiveness. CRTH2-deficient mice had the same degree of allergen-induced airway eosinophilia as wild-type mice, but they did not exhibit a dsRNA-induced increase in eosinophil accumulation. Our data demonstrate that COX-2-dependent production of PGD2 followed by eosinophil recruitment into the airways via a CRTH2 receptor are the major pathogenetic factors responsible for the dsRNA-induced enhancement of airway inflammation and responsiveness.",
author = "Yoshiki Shiraishi and Koichiro Asano and Kyoko Niimi and Koichi Fukunaga and Misa Wakaki and Junko Kagyo and Takahisa Takihara and Soichiro Ueda and Takeshi Nakajima and Tsuyoshi Oguma and Yusuke Suzuki and Tetsuya Shiomi and Koichi Sayama and Shizuko Kagawa and Eiji Ikeda and Hiroyuki Hirai and Kinya Nagata and Masataka Nakamura and Taku Miyasho and Akitoshi Ishizaka",
year = "2008",
month = "1",
day = "1",
language = "English",
volume = "180",
pages = "541--549",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "1",

}

TY - JOUR

T1 - Cyclooxygenase-2/prostaglandin D2/CRTH2 pathway mediates double-stranded RNA-induced enhancement of allergic airway inflammation

AU - Shiraishi, Yoshiki

AU - Asano, Koichiro

AU - Niimi, Kyoko

AU - Fukunaga, Koichi

AU - Wakaki, Misa

AU - Kagyo, Junko

AU - Takihara, Takahisa

AU - Ueda, Soichiro

AU - Nakajima, Takeshi

AU - Oguma, Tsuyoshi

AU - Suzuki, Yusuke

AU - Shiomi, Tetsuya

AU - Sayama, Koichi

AU - Kagawa, Shizuko

AU - Ikeda, Eiji

AU - Hirai, Hiroyuki

AU - Nagata, Kinya

AU - Nakamura, Masataka

AU - Miyasho, Taku

AU - Ishizaka, Akitoshi

PY - 2008/1/1

Y1 - 2008/1/1

N2 - Respiratory RNA viruses responsible for the common cold often worsen airway inflammation and bronchial responsiveness, two characteristic features of human asthma. We studied the effects of dsRNA, a nucleotide synthesized during viral replication, on airway inflammation and bronchial hyperresponsiveness in murine models of asthma. Intratracheal instillation of poly I:C, a synthetic dsRNA, increased the airway eosinophilia and enhanced bronchial hyperresponsiveness to methacholine in OVA-sensitized, exposed rats. These changes were associated with induction of cyclooxygenase-2 (COX-2) expression and COX-2-dependent PGD 2 synthesis in the lungs, particularly in alveolar macrophages. The direct intratracheal instillation of PGD2 enhanced the eosinophilic inflammation in OVA-exposed animals, whereas pretreatment with a dual antagonist against the PGD2 receptor-(CRTH2) and the thromboxane A2 receptor, but not with a thromboxane A2 receptor-specific antagonist, nearly completely eliminated the dsRNA-induced worsening of airway inflammation and bronchial hyperresponsiveness. CRTH2-deficient mice had the same degree of allergen-induced airway eosinophilia as wild-type mice, but they did not exhibit a dsRNA-induced increase in eosinophil accumulation. Our data demonstrate that COX-2-dependent production of PGD2 followed by eosinophil recruitment into the airways via a CRTH2 receptor are the major pathogenetic factors responsible for the dsRNA-induced enhancement of airway inflammation and responsiveness.

AB - Respiratory RNA viruses responsible for the common cold often worsen airway inflammation and bronchial responsiveness, two characteristic features of human asthma. We studied the effects of dsRNA, a nucleotide synthesized during viral replication, on airway inflammation and bronchial hyperresponsiveness in murine models of asthma. Intratracheal instillation of poly I:C, a synthetic dsRNA, increased the airway eosinophilia and enhanced bronchial hyperresponsiveness to methacholine in OVA-sensitized, exposed rats. These changes were associated with induction of cyclooxygenase-2 (COX-2) expression and COX-2-dependent PGD 2 synthesis in the lungs, particularly in alveolar macrophages. The direct intratracheal instillation of PGD2 enhanced the eosinophilic inflammation in OVA-exposed animals, whereas pretreatment with a dual antagonist against the PGD2 receptor-(CRTH2) and the thromboxane A2 receptor, but not with a thromboxane A2 receptor-specific antagonist, nearly completely eliminated the dsRNA-induced worsening of airway inflammation and bronchial hyperresponsiveness. CRTH2-deficient mice had the same degree of allergen-induced airway eosinophilia as wild-type mice, but they did not exhibit a dsRNA-induced increase in eosinophil accumulation. Our data demonstrate that COX-2-dependent production of PGD2 followed by eosinophil recruitment into the airways via a CRTH2 receptor are the major pathogenetic factors responsible for the dsRNA-induced enhancement of airway inflammation and responsiveness.

UR - http://www.scopus.com/inward/record.url?scp=40449106779&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=40449106779&partnerID=8YFLogxK

M3 - Article

VL - 180

SP - 541

EP - 549

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 1

ER -