A common environmental pollutant, 4-nonylphenol, promotes allergic lung inflammation in a murine model of asthma

J. L. Suen, S. H. Hsu, C. H. Hung, Y. S. Chao, C. L. Lee, C. Y. Lin, T. H. Weng, H. S. Yu, S. K. Huang

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background Exposure to environmental hormones, such as alkylphenols, has been suggested to be associated with the development of asthma, but the mechanism of action remains unclear. Objective This study examined the effect of 4-nonylphenol (NP), one of the most important alkylphenols, on conventional dendritic cells (cDCs) and adaptive T-cell responses. It also explored the role of aryl hydrocarbon receptor (AhR) in NP's effect. Methods NP-conditioned bone marrow-derived DCs (BM-DCs) and splenic CD11c+ cDCs were assessed regarding function in a murine model under conditions relevant to route and level of exposure in humans. Results Our results showed that splenic cDCs from NP-exposed mice have potent Th2-skewing ability and secrete increased levels of IL-6 and TNF-α, but not IL-10 and IL-12, at baseline and after stimulation with LPS. Further, bone marrow-derived DCs were cultured in the presence of NP and showed similar cytokine pattern and influenced the antigen-specific T cells secreting significantly less IFN-γ. Importantly, NP-exposed mice developed more severe OVA-induced allergic lung inflammation compared with control group. Interestingly, in a congenic strain of mice carrying low-affinity, ligand-binding mutant AhR (AhRd), NP's effect on DC functions and lung inflammation was not observed in vitro and in vivo. Conclusion These results suggested that NP may disturb physiologic function of DCs through, in part, AhR-dependent mechanisms, supporting the importance of NP exposure on the regulation of DC functions and allergic inflammation.

Original languageEnglish
Pages (from-to)780-787
Number of pages8
JournalAllergy: European Journal of Allergy and Clinical Immunology
Volume68
Issue number6
DOIs
Publication statusPublished - Jun 1 2013
Externally publishedYes

Fingerprint

Environmental Pollutants
Pneumonia
Asthma
Aryl Hydrocarbon Receptors
Dendritic Cells
Bone Marrow
Congenic Mice
T-Lymphocytes
Environmental Exposure
Interleukin-12
Interleukin-10
4-nonylphenol
nonylphenol
Interleukin-6
Hormones
Cytokines
Ligands
Inflammation
Antigens
Control Groups

Keywords

  • 4-nonylphenol
  • allergic asthma
  • aryl hydrocarbon receptor
  • dendritic cell
  • IL-6

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

A common environmental pollutant, 4-nonylphenol, promotes allergic lung inflammation in a murine model of asthma. / Suen, J. L.; Hsu, S. H.; Hung, C. H.; Chao, Y. S.; Lee, C. L.; Lin, C. Y.; Weng, T. H.; Yu, H. S.; Huang, S. K.

In: Allergy: European Journal of Allergy and Clinical Immunology, Vol. 68, No. 6, 01.06.2013, p. 780-787.

Research output: Contribution to journalArticle

Suen, J. L. ; Hsu, S. H. ; Hung, C. H. ; Chao, Y. S. ; Lee, C. L. ; Lin, C. Y. ; Weng, T. H. ; Yu, H. S. ; Huang, S. K. / A common environmental pollutant, 4-nonylphenol, promotes allergic lung inflammation in a murine model of asthma. In: Allergy: European Journal of Allergy and Clinical Immunology. 2013 ; Vol. 68, No. 6. pp. 780-787.
@article{67ad12ce44b34deaa4ed6fb564b67eb5,
title = "A common environmental pollutant, 4-nonylphenol, promotes allergic lung inflammation in a murine model of asthma",
abstract = "Background Exposure to environmental hormones, such as alkylphenols, has been suggested to be associated with the development of asthma, but the mechanism of action remains unclear. Objective This study examined the effect of 4-nonylphenol (NP), one of the most important alkylphenols, on conventional dendritic cells (cDCs) and adaptive T-cell responses. It also explored the role of aryl hydrocarbon receptor (AhR) in NP's effect. Methods NP-conditioned bone marrow-derived DCs (BM-DCs) and splenic CD11c+ cDCs were assessed regarding function in a murine model under conditions relevant to route and level of exposure in humans. Results Our results showed that splenic cDCs from NP-exposed mice have potent Th2-skewing ability and secrete increased levels of IL-6 and TNF-α, but not IL-10 and IL-12, at baseline and after stimulation with LPS. Further, bone marrow-derived DCs were cultured in the presence of NP and showed similar cytokine pattern and influenced the antigen-specific T cells secreting significantly less IFN-γ. Importantly, NP-exposed mice developed more severe OVA-induced allergic lung inflammation compared with control group. Interestingly, in a congenic strain of mice carrying low-affinity, ligand-binding mutant AhR (AhRd), NP's effect on DC functions and lung inflammation was not observed in vitro and in vivo. Conclusion These results suggested that NP may disturb physiologic function of DCs through, in part, AhR-dependent mechanisms, supporting the importance of NP exposure on the regulation of DC functions and allergic inflammation.",
keywords = "4-nonylphenol, allergic asthma, aryl hydrocarbon receptor, dendritic cell, IL-6",
author = "Suen, {J. L.} and Hsu, {S. H.} and Hung, {C. H.} and Chao, {Y. S.} and Lee, {C. L.} and Lin, {C. Y.} and Weng, {T. H.} and Yu, {H. S.} and Huang, {S. K.}",
year = "2013",
month = "6",
day = "1",
doi = "10.1111/all.12156",
language = "English",
volume = "68",
pages = "780--787",
journal = "Allergy: European Journal of Allergy and Clinical Immunology",
issn = "0105-4538",
publisher = "Wiley-Blackwell",
number = "6",

}

TY - JOUR

T1 - A common environmental pollutant, 4-nonylphenol, promotes allergic lung inflammation in a murine model of asthma

AU - Suen, J. L.

AU - Hsu, S. H.

AU - Hung, C. H.

AU - Chao, Y. S.

AU - Lee, C. L.

AU - Lin, C. Y.

AU - Weng, T. H.

AU - Yu, H. S.

AU - Huang, S. K.

PY - 2013/6/1

Y1 - 2013/6/1

N2 - Background Exposure to environmental hormones, such as alkylphenols, has been suggested to be associated with the development of asthma, but the mechanism of action remains unclear. Objective This study examined the effect of 4-nonylphenol (NP), one of the most important alkylphenols, on conventional dendritic cells (cDCs) and adaptive T-cell responses. It also explored the role of aryl hydrocarbon receptor (AhR) in NP's effect. Methods NP-conditioned bone marrow-derived DCs (BM-DCs) and splenic CD11c+ cDCs were assessed regarding function in a murine model under conditions relevant to route and level of exposure in humans. Results Our results showed that splenic cDCs from NP-exposed mice have potent Th2-skewing ability and secrete increased levels of IL-6 and TNF-α, but not IL-10 and IL-12, at baseline and after stimulation with LPS. Further, bone marrow-derived DCs were cultured in the presence of NP and showed similar cytokine pattern and influenced the antigen-specific T cells secreting significantly less IFN-γ. Importantly, NP-exposed mice developed more severe OVA-induced allergic lung inflammation compared with control group. Interestingly, in a congenic strain of mice carrying low-affinity, ligand-binding mutant AhR (AhRd), NP's effect on DC functions and lung inflammation was not observed in vitro and in vivo. Conclusion These results suggested that NP may disturb physiologic function of DCs through, in part, AhR-dependent mechanisms, supporting the importance of NP exposure on the regulation of DC functions and allergic inflammation.

AB - Background Exposure to environmental hormones, such as alkylphenols, has been suggested to be associated with the development of asthma, but the mechanism of action remains unclear. Objective This study examined the effect of 4-nonylphenol (NP), one of the most important alkylphenols, on conventional dendritic cells (cDCs) and adaptive T-cell responses. It also explored the role of aryl hydrocarbon receptor (AhR) in NP's effect. Methods NP-conditioned bone marrow-derived DCs (BM-DCs) and splenic CD11c+ cDCs were assessed regarding function in a murine model under conditions relevant to route and level of exposure in humans. Results Our results showed that splenic cDCs from NP-exposed mice have potent Th2-skewing ability and secrete increased levels of IL-6 and TNF-α, but not IL-10 and IL-12, at baseline and after stimulation with LPS. Further, bone marrow-derived DCs were cultured in the presence of NP and showed similar cytokine pattern and influenced the antigen-specific T cells secreting significantly less IFN-γ. Importantly, NP-exposed mice developed more severe OVA-induced allergic lung inflammation compared with control group. Interestingly, in a congenic strain of mice carrying low-affinity, ligand-binding mutant AhR (AhRd), NP's effect on DC functions and lung inflammation was not observed in vitro and in vivo. Conclusion These results suggested that NP may disturb physiologic function of DCs through, in part, AhR-dependent mechanisms, supporting the importance of NP exposure on the regulation of DC functions and allergic inflammation.

KW - 4-nonylphenol

KW - allergic asthma

KW - aryl hydrocarbon receptor

KW - dendritic cell

KW - IL-6

UR - http://www.scopus.com/inward/record.url?scp=84878108146&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878108146&partnerID=8YFLogxK

U2 - 10.1111/all.12156

DO - 10.1111/all.12156

M3 - Article

C2 - 23621474

AN - SCOPUS:84878108146

VL - 68

SP - 780

EP - 787

JO - Allergy: European Journal of Allergy and Clinical Immunology

JF - Allergy: European Journal of Allergy and Clinical Immunology

SN - 0105-4538

IS - 6

ER -