Institute of Experimental and Clinical Pharmacology and Toxicology, Wilhelmstrasse 56, D-72074 Tübingen, Germany.
Biochem Pharmacol. 2020 Dec;182:114220. doi: 10.1016/j.bcp.2020.114220. Epub 2020 Sep 15.
Inflammation, an old medical problem, is being recognized as an active, well orchestrated biological process. When dysregulated, chronic inflammation may ensue, leading to tissue-dependent diseases. Depending upon the ligand and cellular context, aryl hydrocarbon receptor (AHR) may accelerate or attenuate inflammation and subsequent resolution. Three examples are discussed in which AHR modulates inflammation by a mixture of genomic and non-genomic signaling pathways: (i) AHR-agonistic bacterial virulence factors are leading to both microbial defense and resolution of inflammatory responses. (ii) TCDD-mediated persistent AHR activation initially leads to inflammation by non-genomic signaling, and may potentially lead to chronic inflammation. (iii) AHR may modulate anti-inflammatory actions in obesity-mediated non-alcoholic fatty liver disease (NAFLD): Hepatic lipotoxicity triggers generation of danger-associated molecular patterns (DAMPs) that facilitate the development of hepatitis. AHR is mainly involved in the resolution phase by induction of lipoxin A4 and Il-22. Moderate AHR activation by phytochemicals and microbial AHR ligands may facilitate resolution. In control of inflammation, AHR appears to integrate environmental conditions with coordinated cellular functions.
炎症是一个古老的医学问题，现在被认为是一种活跃的、协调良好的生物学过程。当炎症失调时，可能会导致慢性炎症，进而引发组织依赖性疾病。根据配体和细胞环境的不同，芳香烃受体（AHR）可能会加速或减轻炎症及其后的消退。文中讨论了三个例子，其中 AHR 通过基因组和非基因组信号通路的混合来调节炎症：（i）AHR 激动剂细菌毒力因子既能促进微生物防御，又能促进炎症反应的消退。（ii）TCDD 介导的持续 AHR 激活最初通过非基因组信号导致炎症，并可能导致慢性炎症。（iii）AHR 可能调节肥胖介导的非酒精性脂肪性肝病（NAFLD）中的抗炎作用：肝脂毒性触发危险相关分子模式（DAMPs）的产生，从而促进肝炎的发展。AHR 通过诱导脂氧素 A4 和 Il-22 主要参与消退阶段。植物化学物质和微生物 AHR 配体的适度 AHR 激活可能有助于消退。在炎症控制方面，AHR 似乎将环境条件与协调的细胞功能结合起来。
