Gaspar-Ramírez Octavio, Pérez-Vázquez Francisco J, Salgado-Bustamante Mariana, González-Amaro Roberto, Hernandez-Castro Berenice, Pérez-Maldonado Ivan N
Laboratorio de Toxicología Molecular, Centro de Investigación Aplicada en Ambiente y Salud (CIAAS), Coordinación para la Innovación y Aplicación de la Ciencia y la Tecnología (CIACYT), Universidad Autónoma de San Luis Potosí , San Luis Potosí , México .
J Immunotoxicol. 2015 Jul-Sep;12(3):266-72. doi: 10.3109/1547691X.2014.960108. Epub 2014 Oct 15.
Recent studies have demonstrated that compounds inducing pro-inflammatory cytokines enhance AhR expression. The aim of this study was 2-fold: (1) to determine if two pro-inflammatory compounds, dichlorodiphenyldichloroethylene (DDE) and 2,2',4,4',5,5'-hexa-chlorobiphenyl (PCB 153), independently affect AhR gene expression in peripheral blood mononuclear cells (PBMC); and (2) if affected, to determine whether the mechanism involved was due to AhR activation or to a pro-inflammatory effect of the chemicals. PBMC isolated from healthy individuals were incubated in the presence of DDE (10 µg/ml) and PCB 153 (20 ng/ml) over time and AhR and CYP1A1 expression was assessed with a real-time PCR technique. The results indicated there was over-expression of the AhR mRNA in PBMC when the cells were treated with DDE and PCB 153. No changes in expression levels of CYP1A1 mRNA were found. Importantly, when the cells were exposed to DDE and PCB 153 in the presence of an antagonist of tumor necrosis factor (TNF)-α, the over-expression of AhR was abolished; as expected, the expression of CYP1A1 was unaffected. In conclusion, these studies demonstrated for the first time an increment of AhR expression "in vitro" in PBMC treated with two pro-inflammatory environmental pollutants, DDE and PCB153. Moreover, the over-expression of AhR was dependent of TNFα induced by DDE and PCB 153 and was independent of AhR activation.
最近的研究表明，诱导促炎细胞因子的化合物会增强芳烃受体（AhR）的表达。本研究的目的有两个：（1）确定两种促炎化合物，即二氯二苯二氯乙烯（DDE）和2,2',4,4',5,5'-六氯联苯（PCB 153），是否独立影响外周血单核细胞（PBMC）中的AhR基因表达；（2）如果有影响，确定其涉及的机制是由于AhR激活还是化学物质的促炎作用。从健康个体分离的PBMC在DDE（10μg/ml）和PCB 153（20 ng/ml）存在下随时间孵育，并用实时PCR技术评估AhR和细胞色素P450 1A1（CYP1A1）的表达。结果表明，当细胞用DDE和PCB 153处理时，PBMC中AhR mRNA有过表达。未发现CYP1A1 mRNA表达水平有变化。重要的是，当细胞在肿瘤坏死因子（TNF）-α拮抗剂存在下暴露于DDE和PCB 153时，AhR的过表达被消除；正如预期的那样，CYP1A1的表达未受影响。总之，这些研究首次证明，在用两种促炎环境污染物DDE和PCB153处理的PBMC中，“体外”AhR表达增加。此外，AhR的过表达依赖于DDE和PCB 153诱导的TNFα，且与AhR激活无关。
