Aryl hydrocarbon receptor (AhR) modulates cockroach allergen-induced immune responses through active TGFβ1 release.

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

doi:10.1155/2014/591479

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.

Highlights

Asthma is the most prevalent serious chronic illness of children in the U.S [1]
These findings suggest an increased Aryl hydrocarbon receptor (AhR) expression in fibroblasts from asthmatic patients and possibly from those who are repeatedly exposed to smoking
We investigated the functional significance of AhR in modulating cockroach allergen-induced immune responses by controlling the release of active TGFβ1

Summary

Introduction

Asthma is the most prevalent serious chronic illness of children in the U.S [1]. While it is generally accepted that environmental chemicals and pollutants can contribute to the occurrence and exacerbation of asthma [2,3,4,5], the mechanistic links remain largely unknown. Environmental chemicals and pollutants have been shown to modulate environmental allergen-induced allergic diseases like asthma [6,7,8]. AhR is a multifunctional regulator that senses and responds to environmental stimuli and plays a role in normal cell development and immune regulation. The role of AhR in modulating CRE induced TGFβ1 production was investigated by using AhR agonist, TCDD, antagonist CH122319, and knockdown of AhR. CRE induced TGFβ1 production in fibroblasts was significantly enhanced by TCDD but inhibited by CH122319. TCDD induced active TGFβ1 release was significantly inhibited by LTBP1 knockdown. 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

Methods

Results

Conclusion