Aryl hydrocarbon receptor ligand effects in RBL2H3 cells.
Aryl hydrocarbon receptor ligand effects in RBL2H3 cells.
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DOI：
10.3109/1547691x.2012.661802
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发表时间：
2012-07
影响因子：
3.3
通讯作者：
Turner H
中科院分区：
文献类型：
--
作者：
Maaetoft-Udsen K;Shimoda LM;Frøkiær H;Turner H
芳烃受体（AHR）介导二恶英和异生素代谢的毒性效应。AHR在免疫系统中具有新兴的作用，但其在免疫细胞中的生理配体和功能作用仍然知之甚少。肥大细胞是免疫细胞，其是炎症反应的中心，并且在刺激时释放一系列促炎介质，包括组胺、肥大细胞蛋白酶和促炎细胞因子如IL-6。我们的目的是研究模型肥大细胞中的AHR，并检查推定的和已知的AHR配体，例如，犬尿氨酸、犬尿烯酸（KA）、白藜芦醇、吲哚霉素和紫霉素影响肥大细胞活化和信号传导。我们测试了这些配体的钙信号，脱粒和基因表达。我们的数据表明，AHR存在于三个模型肥大细胞系，和各种已知的和推定的AHR配体调节Cyp 1a 1，AHR的下游基因的基因表达。此外，我们发现，钙内流和肥大细胞分泌反应增强或抑制后，长期治疗与AHR激动剂或拮抗剂，和AHR配体修饰RBL 2 H3细胞脱粒。AHR配体可以长期改变活化的肥大细胞中的细胞因子基因表达，如IL-6所例示。拮抗剂白藜芦醇抑制诱导的IL-6基因表达。虽然KA和犬尿氨酸都是AHR激动剂，但这些配体在脱粒和IL-6表达方面表现不同，表明它们可能在AHR途径之外起作用。这些数据表明，相当复杂的RBL 2 H3反应AHR配体，与我们的理解二恶英的病理和内源性AHR配体的免疫学效应的影响。
The aryl hydrocarbon receptor (AHR) mediates toxic effects of dioxin and xenobiotic metabolism. AHR has an emerging role in the immune system but its physiological ligands and functional role in immunocytes remain poorly understood. Mast cells are immunocytes that are central to inflammatory responses and release a spectrum of pro-inflammatory mediators including histamine, mast cell proteases, and pro-inflammatory cytokines such as IL-6 upon stimulation. Our aim was to investigate the AHR in model mast cells and examine how both putative and known AHR ligands, e.g., kynurenine, kynurenic acid (KA), Resveratrol, indolmycin, and violacein, affect mast cell activation and signaling. We tested these ligands on calcium signaling, degranulation, and gene expression. Our data show that AHR is present in three model mast cell lines, and that various known and putative AHR ligands regulate gene expression of Cyp1a1, a gene down-stream of AHR. Furthermore, we found that calcium influxes and mast cell secretory responses were enhanced or suppressed after chronic treatment with AHR agonists or antagonists, and that AHR ligands modified RBL2H3 cell degranulation. AHR ligands can chronically change cytokine gene expression in activated mast cells, as exemplified by IL-6. The antagonist Resveratrol repressed expression of induced IL-6 gene expression. Though KA and kynurenine are both AHR agonists, these ligands behaved differently in regards to degranulation and IL-6 expression, indicating that they may function outside of AHR pathways. These data suggest considerable complexity in RBL2H3 responses to AHR ligands, with implications for our understanding of both dioxin pathology and the immunological effects of endogenous AHR ligands.