Champion S, Sauzet C, Bremond P, Benbrahim K, Abraldes J, Seree E, Barra Y, Villard P H
IMBE-UMR CNRS 7263, IRD 237 Aix-Marseille Université Campus Timone, Faculté de Pharmacie, 27 boulevard Jean Moulin, 13385 Marseille Cedex 05, France.
ISRN Toxicol. 2013 Oct 21;2013:792452. doi: 10.1155/2013/792452. eCollection 2013.
Recent data suggest that apart from its well-known role in the regulation of xenobiotic metabolizing enzymes, AhR is also involved in inflammation. However, the influence of inflammation on AhR expression remains unknown. Here, we demonstrated that proinflammatory conditions induced by either PMA or IL-1 β enhance AhR expression in Caco-2 cells. This was associated with an increase in AhR promoter activity. By means of directed mutagenesis experiments and the use of proteasome inhibitors, we demonstrated that inflammation-induced AhR expression involved the NF κ B pathway but not AP-1. Moreover, conditioned media from PMA-treated Caco-2 cells were also able to induce AhR expression, and this induction was repressed by anti-IL-1 β blocking antibodies. Similar results were obtained with conditioned media from PMA-treated THP-1 cells. Taken together, these data suggest that AhR could be involved in vivo in an inflammatory loop. AhR was recently suspected to be implicated in inflammatory bowel disease. Our results support this hypothesis and suggest that AhR could be a new target for inflammatory bowel disease patient management.
近期数据表明，除了在调节外源性物质代谢酶方面的众所周知的作用外，芳烃受体（AhR）也参与炎症反应。然而，炎症对AhR表达的影响仍不清楚。在此，我们证明，由佛波酯（PMA）或白细胞介素-1β（IL-1β）诱导的促炎条件可增强Caco-2细胞中AhR的表达。这与AhR启动子活性的增加有关。通过定向诱变实验和使用蛋白酶体抑制剂，我们证明炎症诱导的AhR表达涉及核因子κB（NFκB）途径而非激活蛋白-1（AP-1）。此外，来自经PMA处理的Caco-2细胞的条件培养基也能够诱导AhR表达，并且这种诱导被抗IL-1β阻断抗体所抑制。用来自经PMA处理的THP-1细胞的条件培养基也获得了类似结果。综上所述，这些数据表明AhR可能在体内参与炎症循环。最近怀疑AhR与炎症性肠病有关。我们的结果支持这一假设，并表明AhR可能是炎症性肠病患者管理的新靶点。
