Contrasting roles for the receptor for advanced glycation end-products on structural cells in allergic airway inflammation vs. Airway hyperresponsiveness

Akihiko Taniguchi, Nobuaki Miyahara, Koichi Waseda, Etsuko Kurimoto, Utako Fujii, Yasushi Tanimoto, Mikio Kataoka, Yasuhiko Yamamoto, Erwin W. Gelfand, Hiroshi Yamamoto, Mitsune Tanimoto, Arihiko Kanehiro

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The receptor for advanced glycation end-products (RAGE) is a multiligand receptor that belongs to the immunoglobulin superfamily. RAGE is reported to be involved in various inflammatory disorders; however, studies that address the role of RAGE in allergic airway disease are inconclusive. RAGE-sufficient (RAGE-/-) and RAGE-deficient (RAGE+/+) mice were sensitized to ovalbumin, and airway responses were monitored after ovalbumin challenge. RAGE+/+ mice showed reduced eosinophilic inflammation and goblet cell metaplasia, lower T helper type 2 (Th2) cytokine production from spleen and peribronchial lymph node mononuclear cells, and lower numbers of group 2 innate lymphoid cells in the lung compared with RAGE-/- mice following sensitization and challenge. Experiments using irradiated, chimeric mice showed that the mice expressing RAGE on radio-resistant structural cells but not hematopoietic cells developed allergic airway inflammation; however, the mice expressing RAGE on hematopoietic cells but not structural cells showed reduced airway inflammation. In contrast, absence of RAGE expression on structural cells enhanced innate airway hyperresponsiveness (AHR). In the absence of RAGE, increased interleukin (IL)-33 levels in the lung were detected, and blockade of IL-33 receptor ST2 suppressed innate AHR in RAGE+/+ mice. These data identify the importance of RAGE expressed on lung structural cells in the development of allergic airway inflammation, T helper type 2 cell activation, and group 2 innate lymphoid cell accumulation in the airways. RAGE on lung structural cells also regulated innate AHR, likely through the IL-33-ST2 pathway. Thus manipulating RAGE represents a novel therapeutic target in controlling allergic airway responses.

Original languageEnglish
Pages (from-to)L789-L800
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume309
Issue number8
DOIs
Publication statusPublished - 2015

Fingerprint

Inflammation
Lung
Ovalbumin
Advanced Glycosylation End Product-Specific Receptor
Lymphocytes
Th2 Cells
Goblet Cells
Metaplasia
Radio
Mouse Ager protein
Immunoglobulins
Spleen
Cell Count
Lymph Nodes
Cytokines

Keywords

  • Airway hyperresponsiveness
  • Allergic airway inflammation
  • Asthma
  • RAGE

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology
  • Physiology

Cite this

Contrasting roles for the receptor for advanced glycation end-products on structural cells in allergic airway inflammation vs. Airway hyperresponsiveness. / Taniguchi, Akihiko; Miyahara, Nobuaki; Waseda, Koichi; Kurimoto, Etsuko; Fujii, Utako; Tanimoto, Yasushi; Kataoka, Mikio; Yamamoto, Yasuhiko; Gelfand, Erwin W.; Yamamoto, Hiroshi; Tanimoto, Mitsune; Kanehiro, Arihiko.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 309, No. 8, 2015, p. L789-L800.

Research output: Contribution to journalArticle

Taniguchi, Akihiko ; Miyahara, Nobuaki ; Waseda, Koichi ; Kurimoto, Etsuko ; Fujii, Utako ; Tanimoto, Yasushi ; Kataoka, Mikio ; Yamamoto, Yasuhiko ; Gelfand, Erwin W. ; Yamamoto, Hiroshi ; Tanimoto, Mitsune ; Kanehiro, Arihiko. / Contrasting roles for the receptor for advanced glycation end-products on structural cells in allergic airway inflammation vs. Airway hyperresponsiveness. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2015 ; Vol. 309, No. 8. pp. L789-L800.
@article{2c900b441762495c85dfa9ef1f005dbd,
title = "Contrasting roles for the receptor for advanced glycation end-products on structural cells in allergic airway inflammation vs. Airway hyperresponsiveness",
abstract = "The receptor for advanced glycation end-products (RAGE) is a multiligand receptor that belongs to the immunoglobulin superfamily. RAGE is reported to be involved in various inflammatory disorders; however, studies that address the role of RAGE in allergic airway disease are inconclusive. RAGE-sufficient (RAGE-/-) and RAGE-deficient (RAGE+/+) mice were sensitized to ovalbumin, and airway responses were monitored after ovalbumin challenge. RAGE+/+ mice showed reduced eosinophilic inflammation and goblet cell metaplasia, lower T helper type 2 (Th2) cytokine production from spleen and peribronchial lymph node mononuclear cells, and lower numbers of group 2 innate lymphoid cells in the lung compared with RAGE-/- mice following sensitization and challenge. Experiments using irradiated, chimeric mice showed that the mice expressing RAGE on radio-resistant structural cells but not hematopoietic cells developed allergic airway inflammation; however, the mice expressing RAGE on hematopoietic cells but not structural cells showed reduced airway inflammation. In contrast, absence of RAGE expression on structural cells enhanced innate airway hyperresponsiveness (AHR). In the absence of RAGE, increased interleukin (IL)-33 levels in the lung were detected, and blockade of IL-33 receptor ST2 suppressed innate AHR in RAGE+/+ mice. These data identify the importance of RAGE expressed on lung structural cells in the development of allergic airway inflammation, T helper type 2 cell activation, and group 2 innate lymphoid cell accumulation in the airways. RAGE on lung structural cells also regulated innate AHR, likely through the IL-33-ST2 pathway. Thus manipulating RAGE represents a novel therapeutic target in controlling allergic airway responses.",
keywords = "Airway hyperresponsiveness, Allergic airway inflammation, Asthma, RAGE",
author = "Akihiko Taniguchi and Nobuaki Miyahara and Koichi Waseda and Etsuko Kurimoto and Utako Fujii and Yasushi Tanimoto and Mikio Kataoka and Yasuhiko Yamamoto and Gelfand, {Erwin W.} and Hiroshi Yamamoto and Mitsune Tanimoto and Arihiko Kanehiro",
year = "2015",
doi = "10.1152/ajplung.00087.2015",
language = "English",
volume = "309",
pages = "L789--L800",
journal = "American Journal of Physiology - Lung Cellular and Molecular Physiology",
issn = "1040-0605",
publisher = "American Physiological Society",
number = "8",

}

TY - JOUR

T1 - Contrasting roles for the receptor for advanced glycation end-products on structural cells in allergic airway inflammation vs. Airway hyperresponsiveness

AU - Taniguchi, Akihiko

AU - Miyahara, Nobuaki

AU - Waseda, Koichi

AU - Kurimoto, Etsuko

AU - Fujii, Utako

AU - Tanimoto, Yasushi

AU - Kataoka, Mikio

AU - Yamamoto, Yasuhiko

AU - Gelfand, Erwin W.

AU - Yamamoto, Hiroshi

AU - Tanimoto, Mitsune

AU - Kanehiro, Arihiko

PY - 2015

Y1 - 2015

N2 - The receptor for advanced glycation end-products (RAGE) is a multiligand receptor that belongs to the immunoglobulin superfamily. RAGE is reported to be involved in various inflammatory disorders; however, studies that address the role of RAGE in allergic airway disease are inconclusive. RAGE-sufficient (RAGE-/-) and RAGE-deficient (RAGE+/+) mice were sensitized to ovalbumin, and airway responses were monitored after ovalbumin challenge. RAGE+/+ mice showed reduced eosinophilic inflammation and goblet cell metaplasia, lower T helper type 2 (Th2) cytokine production from spleen and peribronchial lymph node mononuclear cells, and lower numbers of group 2 innate lymphoid cells in the lung compared with RAGE-/- mice following sensitization and challenge. Experiments using irradiated, chimeric mice showed that the mice expressing RAGE on radio-resistant structural cells but not hematopoietic cells developed allergic airway inflammation; however, the mice expressing RAGE on hematopoietic cells but not structural cells showed reduced airway inflammation. In contrast, absence of RAGE expression on structural cells enhanced innate airway hyperresponsiveness (AHR). In the absence of RAGE, increased interleukin (IL)-33 levels in the lung were detected, and blockade of IL-33 receptor ST2 suppressed innate AHR in RAGE+/+ mice. These data identify the importance of RAGE expressed on lung structural cells in the development of allergic airway inflammation, T helper type 2 cell activation, and group 2 innate lymphoid cell accumulation in the airways. RAGE on lung structural cells also regulated innate AHR, likely through the IL-33-ST2 pathway. Thus manipulating RAGE represents a novel therapeutic target in controlling allergic airway responses.

AB - The receptor for advanced glycation end-products (RAGE) is a multiligand receptor that belongs to the immunoglobulin superfamily. RAGE is reported to be involved in various inflammatory disorders; however, studies that address the role of RAGE in allergic airway disease are inconclusive. RAGE-sufficient (RAGE-/-) and RAGE-deficient (RAGE+/+) mice were sensitized to ovalbumin, and airway responses were monitored after ovalbumin challenge. RAGE+/+ mice showed reduced eosinophilic inflammation and goblet cell metaplasia, lower T helper type 2 (Th2) cytokine production from spleen and peribronchial lymph node mononuclear cells, and lower numbers of group 2 innate lymphoid cells in the lung compared with RAGE-/- mice following sensitization and challenge. Experiments using irradiated, chimeric mice showed that the mice expressing RAGE on radio-resistant structural cells but not hematopoietic cells developed allergic airway inflammation; however, the mice expressing RAGE on hematopoietic cells but not structural cells showed reduced airway inflammation. In contrast, absence of RAGE expression on structural cells enhanced innate airway hyperresponsiveness (AHR). In the absence of RAGE, increased interleukin (IL)-33 levels in the lung were detected, and blockade of IL-33 receptor ST2 suppressed innate AHR in RAGE+/+ mice. These data identify the importance of RAGE expressed on lung structural cells in the development of allergic airway inflammation, T helper type 2 cell activation, and group 2 innate lymphoid cell accumulation in the airways. RAGE on lung structural cells also regulated innate AHR, likely through the IL-33-ST2 pathway. Thus manipulating RAGE represents a novel therapeutic target in controlling allergic airway responses.

KW - Airway hyperresponsiveness

KW - Allergic airway inflammation

KW - Asthma

KW - RAGE

UR - http://www.scopus.com/inward/record.url?scp=84944456948&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84944456948&partnerID=8YFLogxK

U2 - 10.1152/ajplung.00087.2015

DO - 10.1152/ajplung.00087.2015

M3 - Article

VL - 309

SP - L789-L800

JO - American Journal of Physiology - Lung Cellular and Molecular Physiology

JF - American Journal of Physiology - Lung Cellular and Molecular Physiology

SN - 1040-0605

IS - 8

ER -