Aryl Hydrocarbon Receptor AhR Modulates Cockroach Allergen-Induced Immune Responses through Active TGFβ1 ReleaseReport as inadecuate




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Mediators of InflammationVolume 2014 2014, Article ID 591479, 13 pages

Research Article

Johns Hopkins Asthma and Allergy Center, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA

Sher-i-Kashmir Institute of Medical Sciences, Medical College SKIMS, Kashmir 190001, India

Received 13 December 2013; Revised 14 February 2014; Accepted 15 February 2014; Published 26 March 2014

Academic Editor: Shaoheng He

Copyright © 2014 Yufeng Zhou et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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.





Author: Yufeng Zhou, Sarah Mirza, Ting Xu, Priya Tripathi, Beverly Plunkett, Allen Myers, and Peisong Gao

Source: https://www.hindawi.com/



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