Aryl Hydrocarbon Receptor (AhR) Modulates Cockroach Allergen-Induced Immune Responses through Active TGFβ1 Release

Background. Aryl hydrocarbon receptor (AhR), a multifunctional regulator that senses and responds to environmental stimuli, plays a role in normal cell development and immune regulation. Recent evidence supports a significant link between environmental exposure and AhR in the development of allergic...

Full description

Saved in:
Bibliographic Details
Main Authors: Yufeng Zhou, Sarah Mirza, Ting Xu, Priya Tripathi, Beverly Plunkett, Allen Myers, Peisong Gao
Format: Article
Language:English
Published: Wiley 2014-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2014/591479
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832549280333692928
author Yufeng Zhou
Sarah Mirza
Ting Xu
Priya Tripathi
Beverly Plunkett
Allen Myers
Peisong Gao
author_facet Yufeng Zhou
Sarah Mirza
Ting Xu
Priya Tripathi
Beverly Plunkett
Allen Myers
Peisong Gao
author_sort Yufeng Zhou
collection DOAJ
description Background. Aryl hydrocarbon receptor (AhR), a multifunctional regulator that senses and responds to environmental stimuli, plays a role in normal cell development and immune regulation. Recent evidence supports a significant link between environmental exposure and AhR in the development of allergic diseases. We sought to investigate whether AhR plays a role in mediating cockroach allergen-induced allergic immune responses. Methods. AhR expression in human lung fibroblasts from asthmatic and healthy individuals and in cockroach extract (CRE) treated human lung fibroblasts (WI-38) was examined. The role of AhR in modulating CRE induced TGFβ1 production was investigated by using AhR agonist, TCDD, antagonist CH122319, and knockdown of AhR. The role of latent TGFβ1 binding protein-1 (LTBP1) in mediating TCDD induced active TGFβ1 release was also examined. Results. AhR expression was higher in airway fibroblasts from asthmatic subjects as compared to healthy controls. AhR in fibroblasts was activated by TCDD with an increased expression of cyp1a1 and cyp1b1. Increased AhR expression was observed in CRE-treated fibroblasts. Importantly, CRE induced TGFβ1 production in fibroblasts was significantly enhanced by TCDD but inhibited by CH122319. Reduced TGFβ1 production was further confirmed in fibroblasts with AhR knockdown. Moreover, AhR knockdown inhibited CRE induced fibroblast differentiation. Furthermore, TCDD induced active TGFβ1 release was significantly inhibited by LTBP1 knockdown. Conclusion. These results provide evidence for the role of AhR in modulating cockroach allergen-induced immune responses through controlling the active TGFβ1 release, suggesting a possible synergistic effect between exposure to allergens and environmental chemicals on the development of allergic diseases.
format Article
id doaj-art-031f6ffeed7a4e4f9af83f002be6ed8c
institution Kabale University
issn 0962-9351
1466-1861
language English
publishDate 2014-01-01
publisher Wiley
record_format Article
series Mediators of Inflammation
spelling doaj-art-031f6ffeed7a4e4f9af83f002be6ed8c2025-02-03T06:11:40ZengWileyMediators of Inflammation0962-93511466-18612014-01-01201410.1155/2014/591479591479Aryl Hydrocarbon Receptor (AhR) Modulates Cockroach Allergen-Induced Immune Responses through Active TGFβ1 ReleaseYufeng Zhou0Sarah Mirza1Ting Xu2Priya Tripathi3Beverly Plunkett4Allen Myers5Peisong Gao6Johns Hopkins Asthma and Allergy Center, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USAJohns Hopkins Asthma and Allergy Center, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USAJohns Hopkins Asthma and Allergy Center, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USAJohns Hopkins Asthma and Allergy Center, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USAJohns Hopkins Asthma and Allergy Center, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USAJohns Hopkins Asthma and Allergy Center, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USAJohns Hopkins Asthma and Allergy Center, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USABackground. Aryl hydrocarbon receptor (AhR), a multifunctional regulator that senses and responds to environmental stimuli, plays a role in normal cell development and immune regulation. Recent evidence supports a significant link between environmental exposure and AhR in the development of allergic diseases. We sought to investigate whether AhR plays a role in mediating cockroach allergen-induced allergic immune responses. Methods. AhR expression in human lung fibroblasts from asthmatic and healthy individuals and in cockroach extract (CRE) treated human lung fibroblasts (WI-38) was examined. The role of AhR in modulating CRE induced TGFβ1 production was investigated by using AhR agonist, TCDD, antagonist CH122319, and knockdown of AhR. The role of latent TGFβ1 binding protein-1 (LTBP1) in mediating TCDD induced active TGFβ1 release was also examined. Results. AhR expression was higher in airway fibroblasts from asthmatic subjects as compared to healthy controls. AhR in fibroblasts was activated by TCDD with an increased expression of cyp1a1 and cyp1b1. Increased AhR expression was observed in CRE-treated fibroblasts. Importantly, CRE induced TGFβ1 production in fibroblasts was significantly enhanced by TCDD but inhibited by CH122319. Reduced TGFβ1 production was further confirmed in fibroblasts with AhR knockdown. Moreover, AhR knockdown inhibited CRE induced fibroblast differentiation. Furthermore, TCDD induced active TGFβ1 release was significantly inhibited by LTBP1 knockdown. Conclusion. These results provide evidence for the role of AhR in modulating cockroach allergen-induced immune responses through controlling the active TGFβ1 release, suggesting a possible synergistic effect between exposure to allergens and environmental chemicals on the development of allergic diseases.http://dx.doi.org/10.1155/2014/591479
spellingShingle Yufeng Zhou
Sarah Mirza
Ting Xu
Priya Tripathi
Beverly Plunkett
Allen Myers
Peisong Gao
Aryl Hydrocarbon Receptor (AhR) Modulates Cockroach Allergen-Induced Immune Responses through Active TGFβ1 Release
Mediators of Inflammation
title Aryl Hydrocarbon Receptor (AhR) Modulates Cockroach Allergen-Induced Immune Responses through Active TGFβ1 Release
title_full Aryl Hydrocarbon Receptor (AhR) Modulates Cockroach Allergen-Induced Immune Responses through Active TGFβ1 Release
title_fullStr Aryl Hydrocarbon Receptor (AhR) Modulates Cockroach Allergen-Induced Immune Responses through Active TGFβ1 Release
title_full_unstemmed Aryl Hydrocarbon Receptor (AhR) Modulates Cockroach Allergen-Induced Immune Responses through Active TGFβ1 Release
title_short Aryl Hydrocarbon Receptor (AhR) Modulates Cockroach Allergen-Induced Immune Responses through Active TGFβ1 Release
title_sort aryl hydrocarbon receptor ahr modulates cockroach allergen induced immune responses through active tgfβ1 release
url http://dx.doi.org/10.1155/2014/591479
work_keys_str_mv AT yufengzhou arylhydrocarbonreceptorahrmodulatescockroachallergeninducedimmuneresponsesthroughactivetgfb1release
AT sarahmirza arylhydrocarbonreceptorahrmodulatescockroachallergeninducedimmuneresponsesthroughactivetgfb1release
AT tingxu arylhydrocarbonreceptorahrmodulatescockroachallergeninducedimmuneresponsesthroughactivetgfb1release
AT priyatripathi arylhydrocarbonreceptorahrmodulatescockroachallergeninducedimmuneresponsesthroughactivetgfb1release
AT beverlyplunkett arylhydrocarbonreceptorahrmodulatescockroachallergeninducedimmuneresponsesthroughactivetgfb1release
AT allenmyers arylhydrocarbonreceptorahrmodulatescockroachallergeninducedimmuneresponsesthroughactivetgfb1release
AT peisonggao arylhydrocarbonreceptorahrmodulatescockroachallergeninducedimmuneresponsesthroughactivetgfb1release