Center for Health and the Environment, University of California Davis, One Shields Avenue, Davis, CA 95616, USA.
Biochem Biophys Res Commun. 2011 Jul 1;410(2):358-63. doi: 10.1016/j.bbrc.2011.06.018. Epub 2011 Jun 12.
Recent reports suggest the participation of the aryl hydrocarbon receptor (AhR) in the induction mechanism of the NF-κB signaling pathway. In the current study we challenged C57BL/6 wild-type (WT) and AhR deficient (AhR(-/-)) mice with bacterial lipopolysaccharide (LPS) to investigate the role of the AhR in expression profiles of LPS and NF-κB target genes. Further, we analyzed the effect of LPS on the DNA binding activity of NF-κB, C/EBP and AP-1 transcription factors in liver and lung from WT and AhR(-/-) mice. The results show that the LPS-induced expression of several target genes was impaired in AhR(-/-) mice compared to WT mice. Depending on the target gene, the target tissue as well as the time of treatment, the deficiency of AhR may cause an inhibition or increase of the LPS-induced gene expression. The binding activity of NF-κB, C/EBP and AP-1 transcription factors was also affected in a time- and tissue-dependent manner. The current study shows that the AhR is implemented in LPS-induced inflammatory gene expression in vivo even in the absence of exogenous ligands of the AhR. The main implication of this finding is that the AhR functions in Toll-like receptor (TLR) and NF-κB signaling after activation by a classical stimulus, such as LPS.
最近的报告表明，芳香烃受体 (AhR) 参与了 NF-κB 信号通路的诱导机制。在本研究中，我们用细菌脂多糖 (LPS) 对 C57BL/6 野生型 (WT) 和 AhR 缺失型 (AhR(-/-)) 小鼠进行了挑战，以研究 AhR 在 LPS 和 NF-κB 靶基因表达谱中的作用。此外，我们分析了 LPS 对 WT 和 AhR(-/-) 小鼠肝和肺中 NF-κB、C/EBP 和 AP-1 转录因子的 DNA 结合活性的影响。结果表明，与 WT 小鼠相比，LPS 诱导的几种靶基因在 AhR(-/-) 小鼠中的表达受损。取决于靶基因、靶组织以及处理时间，AhR 的缺失可能导致 LPS 诱导的基因表达受到抑制或增加。NF-κB、C/EBP 和 AP-1 转录因子的结合活性也以时间和组织依赖的方式受到影响。本研究表明，即使没有 AhR 的外源性配体，AhR 也参与了 LPS 诱导的体内炎症基因表达。这一发现的主要意义是，AhR 在 TLR 和 NF-κB 信号转导中起作用，在受到经典刺激（如 LPS）激活后。
