Zhou Yufeng, Mirza Sarah, Xu Ting, Tripathi Priya, Plunkett Beverly, Myers Allen, Gao Peisong
Johns Hopkins Asthma and Allergy Center, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
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.
Mediators Inflamm. 2014;2014:591479. doi: 10.1155/2014/591479. Epub 2014 Mar 26.
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.
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.
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.
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.
芳烃受体（AhR）是一种多功能调节因子，可感知并响应环境刺激，在正常细胞发育和免疫调节中发挥作用。最近的证据支持环境暴露与AhR在过敏性疾病发展中的重要联系。我们试图研究AhR是否在介导蟑螂过敏原诱导的过敏性免疫反应中发挥作用。
检测哮喘患者和健康个体的人肺成纤维细胞以及蟑螂提取物（CRE）处理的人肺成纤维细胞（WI-38）中AhR的表达。通过使用AhR激动剂TCDD、拮抗剂CH122319和敲低AhR来研究AhR在调节CRE诱导的TGFβ1产生中的作用。还研究了潜伏性TGFβ1结合蛋白-1（LTBP1）在介导TCDD诱导的活性TGFβ1释放中的作用。
与健康对照相比，哮喘患者气道成纤维细胞中AhR的表达更高。成纤维细胞中的AhR被TCDD激活，cyp1a1和cyp1b1的表达增加。在CRE处理的成纤维细胞中观察到AhR表达增加。重要的是，TCDD显著增强了CRE诱导的成纤维细胞中TGFβ1的产生，但被CH122319抑制。在敲低AhR的成纤维细胞中进一步证实了TGFβ1产生的减少。此外，AhR敲低抑制了CRE诱导的成纤维细胞分化。此外，LTBP1敲低显著抑制了TCDD诱导的活性TGFβ1释放。
这些结果为AhR通过控制活性TGFβ1释放来调节蟑螂过敏原诱导的免疫反应的作用提供了证据，表明过敏原暴露与环境化学物质在过敏性疾病发展中可能存在协同效应。
