Tian Yanan
Interdisciplinary Graduate Program of Toxicology, Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843-4466, USA.
Biochem Pharmacol. 2009 Feb 15;77(4):670-80. doi: 10.1016/j.bcp.2008.10.023. Epub 2008 Oct 28.
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that belongs to the basic helix-loop-helix/Per-ARNT-Sim (bHLH-PAS) family. Its ligands include many natural and synthetic compounds, some of which, such as polyhalogenated aromatic hydrocarbons and polycyclic aromatic hydrocarbons, are important environmental contaminants. NF-kappaB is a pleiotropic factor that regulates many physiological and pathophysiological processes including the immune and inflammatory responses. In the past decade, accumulating evidence suggests close interactions between AhR and NF-kappaB pathways, and these interactions are potentially important mechanisms for many pathological processes such as the chemical-induced immune dysfunctions, carcinogenesis and alteration of xenobiotic metabolism and disposition. AhR-NF-kappaB interaction has become a mechanistic linchpin linking certain pathological responses induced by environmental insults. Furthermore, the AhR-NF-kappaB interaction provides basis for therapeutic applications of certain AhR ligands to treat human diseases. The effects of AhR-NF-kappaB on the epigenome are an important area that is not well understood. In this review, I highlight current research regarding the AhR-NF-kappaB(RelA) interactions with emphasis on the epigenetic impacts of these interactions on chromatin modifications and transcription elongation control.
芳烃受体(AhR)是一种配体激活的转录因子,属于碱性螺旋-环-螺旋/Per-ARNT-Sim(bHLH-PAS)家族。其配体包括许多天然和合成化合物,其中一些,如多卤代芳烃和多环芳烃,是重要的环境污染物。核因子κB(NF-κB)是一种多效性因子,可调节包括免疫和炎症反应在内的许多生理和病理生理过程。在过去十年中,越来越多的证据表明AhR和NF-κB信号通路之间存在密切相互作用,并且这些相互作用是许多病理过程的潜在重要机制,如化学物质诱导的免疫功能障碍、致癌作用以及外源性物质代谢和处置的改变。AhR-NF-κB相互作用已成为连接环境损伤诱导的某些病理反应的机制关键。此外,AhR-NF-κB相互作用为某些AhR配体治疗人类疾病的治疗应用提供了基础。AhR-NF-κB对表观基因组的影响是一个尚未得到充分理解的重要领域。在这篇综述中,我重点介绍了关于AhR-NF-κB(RelA)相互作用的当前研究,重点是这些相互作用对染色质修饰和转录延伸控制的表观遗传影响。