Lipopolysaccharide induces proinflammatory cytokines and chemokines in experimental otitis media through the prostaglandin D2 receptor (DP)-dependent pathway

M. Eguchi, Shin Kariya, M. Okano, Takaya Higaki, S. Makihara, T. Fujiwara, K. Nagata, H. Hirai, S. Narumiya, M. Nakamura, Kazunori Nishizaki

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Otitis media is one of the most common and intractable ear diseases, and is the major cause of hearing loss, especially in children. Multiple factors affect the onset or development of otitis media. Prostaglandin D2 is the major prostanoid involved in infection and allergy. However, the role of prostaglandin D2 and prostaglandin D2 receptors on the pathogenesis of otitis media remains to be determined. Recent studies show that D prostanoid receptor (DP) and chemoattractant receptor-homologous molecule expressed on T helper type 2 (Th2) cells (CRTH2) are major prostaglandin D2 receptors. In this study, homozygous DP single gene-deficient (DP-/-) mice, CRTH2 single gene-deficient (CRTH2-/-) mice and DP/CRTH2 double gene-deficient (DP-/- CRTH2-/-) mice were used to investigate the role of prostaglandin D2 and its receptors in otitis media. We demonstrate that prostaglandin D2 is induced by lipopolysaccharide (LPS), a major component of Gram-negative bacteria, and that transtympanic injection of prostaglandin D2 up-regulates macrophage inflammatory protein 2 (MIP-2), interleukin (IL)-1β and IL-6 in the middle ear. We also show that middle ear inflammatory reactions, including infiltration of inflammatory cells and expression of MIP-2, IL-1β and IL-6 induced by LPS, are reduced significantly in DP-/- mice and DP-/- CRTH2-/- mice. CRTH2-/- mice display inflammatory reactions similar to wild-type mice. These findings indicate that prostaglandin D2 may play significant roles in LPS-induced experimental otitis media via DP.

Original languageEnglish
Pages (from-to)260-269
Number of pages10
JournalClinical and Experimental Immunology
Volume163
Issue number2
DOIs
Publication statusPublished - Feb 2011

Fingerprint

Otitis Media
Chemokines
Prostaglandins
Lipopolysaccharides
Prostaglandin D2
Cytokines
Chemokine CXCL2
Middle Ear
Interleukin-1
Interleukin-6
Formyl Peptide Receptor
Genes
Ear Diseases
Th2 Cells
prostaglandin D2 receptor
Gram-Negative Bacteria
Hearing Loss
Hypersensitivity
Up-Regulation
Injections

Keywords

  • Animal models/studies-mice/rats
  • Cytokine/interleukin/chemokine receptors
  • Ear immunology/disease
  • Eicosanoids
  • Inflammation/inflammatory mediators
  • Otitis media

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Lipopolysaccharide induces proinflammatory cytokines and chemokines in experimental otitis media through the prostaglandin D2 receptor (DP)-dependent pathway. / Eguchi, M.; Kariya, Shin; Okano, M.; Higaki, Takaya; Makihara, S.; Fujiwara, T.; Nagata, K.; Hirai, H.; Narumiya, S.; Nakamura, M.; Nishizaki, Kazunori.

In: Clinical and Experimental Immunology, Vol. 163, No. 2, 02.2011, p. 260-269.

Research output: Contribution to journalArticle

@article{ba9f77aa1bdc438ca95c700b5b0ac7a3,
title = "Lipopolysaccharide induces proinflammatory cytokines and chemokines in experimental otitis media through the prostaglandin D2 receptor (DP)-dependent pathway",
abstract = "Otitis media is one of the most common and intractable ear diseases, and is the major cause of hearing loss, especially in children. Multiple factors affect the onset or development of otitis media. Prostaglandin D2 is the major prostanoid involved in infection and allergy. However, the role of prostaglandin D2 and prostaglandin D2 receptors on the pathogenesis of otitis media remains to be determined. Recent studies show that D prostanoid receptor (DP) and chemoattractant receptor-homologous molecule expressed on T helper type 2 (Th2) cells (CRTH2) are major prostaglandin D2 receptors. In this study, homozygous DP single gene-deficient (DP-/-) mice, CRTH2 single gene-deficient (CRTH2-/-) mice and DP/CRTH2 double gene-deficient (DP-/- CRTH2-/-) mice were used to investigate the role of prostaglandin D2 and its receptors in otitis media. We demonstrate that prostaglandin D2 is induced by lipopolysaccharide (LPS), a major component of Gram-negative bacteria, and that transtympanic injection of prostaglandin D2 up-regulates macrophage inflammatory protein 2 (MIP-2), interleukin (IL)-1β and IL-6 in the middle ear. We also show that middle ear inflammatory reactions, including infiltration of inflammatory cells and expression of MIP-2, IL-1β and IL-6 induced by LPS, are reduced significantly in DP-/- mice and DP-/- CRTH2-/- mice. CRTH2-/- mice display inflammatory reactions similar to wild-type mice. These findings indicate that prostaglandin D2 may play significant roles in LPS-induced experimental otitis media via DP.",
keywords = "Animal models/studies-mice/rats, Cytokine/interleukin/chemokine receptors, Ear immunology/disease, Eicosanoids, Inflammation/inflammatory mediators, Otitis media",
author = "M. Eguchi and Shin Kariya and M. Okano and Takaya Higaki and S. Makihara and T. Fujiwara and K. Nagata and H. Hirai and S. Narumiya and M. Nakamura and Kazunori Nishizaki",
year = "2011",
month = "2",
doi = "10.1111/j.1365-2249.2010.04292.x",
language = "English",
volume = "163",
pages = "260--269",
journal = "Clinical and Experimental Immunology",
issn = "0009-9104",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - Lipopolysaccharide induces proinflammatory cytokines and chemokines in experimental otitis media through the prostaglandin D2 receptor (DP)-dependent pathway

AU - Eguchi, M.

AU - Kariya, Shin

AU - Okano, M.

AU - Higaki, Takaya

AU - Makihara, S.

AU - Fujiwara, T.

AU - Nagata, K.

AU - Hirai, H.

AU - Narumiya, S.

AU - Nakamura, M.

AU - Nishizaki, Kazunori

PY - 2011/2

Y1 - 2011/2

N2 - Otitis media is one of the most common and intractable ear diseases, and is the major cause of hearing loss, especially in children. Multiple factors affect the onset or development of otitis media. Prostaglandin D2 is the major prostanoid involved in infection and allergy. However, the role of prostaglandin D2 and prostaglandin D2 receptors on the pathogenesis of otitis media remains to be determined. Recent studies show that D prostanoid receptor (DP) and chemoattractant receptor-homologous molecule expressed on T helper type 2 (Th2) cells (CRTH2) are major prostaglandin D2 receptors. In this study, homozygous DP single gene-deficient (DP-/-) mice, CRTH2 single gene-deficient (CRTH2-/-) mice and DP/CRTH2 double gene-deficient (DP-/- CRTH2-/-) mice were used to investigate the role of prostaglandin D2 and its receptors in otitis media. We demonstrate that prostaglandin D2 is induced by lipopolysaccharide (LPS), a major component of Gram-negative bacteria, and that transtympanic injection of prostaglandin D2 up-regulates macrophage inflammatory protein 2 (MIP-2), interleukin (IL)-1β and IL-6 in the middle ear. We also show that middle ear inflammatory reactions, including infiltration of inflammatory cells and expression of MIP-2, IL-1β and IL-6 induced by LPS, are reduced significantly in DP-/- mice and DP-/- CRTH2-/- mice. CRTH2-/- mice display inflammatory reactions similar to wild-type mice. These findings indicate that prostaglandin D2 may play significant roles in LPS-induced experimental otitis media via DP.

AB - Otitis media is one of the most common and intractable ear diseases, and is the major cause of hearing loss, especially in children. Multiple factors affect the onset or development of otitis media. Prostaglandin D2 is the major prostanoid involved in infection and allergy. However, the role of prostaglandin D2 and prostaglandin D2 receptors on the pathogenesis of otitis media remains to be determined. Recent studies show that D prostanoid receptor (DP) and chemoattractant receptor-homologous molecule expressed on T helper type 2 (Th2) cells (CRTH2) are major prostaglandin D2 receptors. In this study, homozygous DP single gene-deficient (DP-/-) mice, CRTH2 single gene-deficient (CRTH2-/-) mice and DP/CRTH2 double gene-deficient (DP-/- CRTH2-/-) mice were used to investigate the role of prostaglandin D2 and its receptors in otitis media. We demonstrate that prostaglandin D2 is induced by lipopolysaccharide (LPS), a major component of Gram-negative bacteria, and that transtympanic injection of prostaglandin D2 up-regulates macrophage inflammatory protein 2 (MIP-2), interleukin (IL)-1β and IL-6 in the middle ear. We also show that middle ear inflammatory reactions, including infiltration of inflammatory cells and expression of MIP-2, IL-1β and IL-6 induced by LPS, are reduced significantly in DP-/- mice and DP-/- CRTH2-/- mice. CRTH2-/- mice display inflammatory reactions similar to wild-type mice. These findings indicate that prostaglandin D2 may play significant roles in LPS-induced experimental otitis media via DP.

KW - Animal models/studies-mice/rats

KW - Cytokine/interleukin/chemokine receptors

KW - Ear immunology/disease

KW - Eicosanoids

KW - Inflammation/inflammatory mediators

KW - Otitis media

UR - http://www.scopus.com/inward/record.url?scp=78650844292&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78650844292&partnerID=8YFLogxK

U2 - 10.1111/j.1365-2249.2010.04292.x

DO - 10.1111/j.1365-2249.2010.04292.x

M3 - Article

C2 - 21166666

AN - SCOPUS:78650844292

VL - 163

SP - 260

EP - 269

JO - Clinical and Experimental Immunology

JF - Clinical and Experimental Immunology

SN - 0009-9104

IS - 2

ER -