Institute of Experimental and Clinical Pharmacology and Toxicology, Wilhelmstrasse 56, D-72074 Tübingen, Germany.
Biochem Pharmacol. 2021 Feb;184:114346. doi: 10.1016/j.bcp.2020.114346. Epub 2020 Nov 21.
Aryl hydrocarbon receptor (AHR) has been characterized as multifunctional sensor, integrator and ligand-activated transcription factor of the bHLH/PAS family. Regulation of inflammatory diseases and energy metabolism are among the putative functions of AHR. Challenges in AHR research include marked species differences, and cell, tissue and context dependence of AHR functions. The commentary is focused on AHR's role in the integration between energy expenditure and microbial and non-infectious inflammation, the latter exemplified by obesity-mediated nonalcoholic fatty liver disease. One of the mechanisms controlling energy-consuming inflammation is represented by a signalsome that is involved in retinoic acid-triggered neutrophil differentiation and regulation of the NADPH oxidase complex (NOX). Established signalsome components are AHR, CD38, multiple protein kinases and adaptors. To prevent chronic inflammatory diseases, the complex interplay between a range of inflammatory responses and energy expenditure must be precisely regulated. Surviving an infection requires both pathogen clearance and tissue protection from inflammatory damage. Defenses are energy-consuming anabolic programs. Therefore, anti-inflammatory, catabolic tolerance programs by metabolic reprogramming of macrophages have evolved. Therapeutic options of AHR agonists to reduce chronic inflammatory diseases are discussed.
芳烃受体 (AHR) 已被描述为具有多功能的传感器、整合器和 bHLH/PAS 家族的配体激活转录因子。AHR 的假定功能包括调节炎症性疾病和能量代谢。AHR 研究中的挑战包括明显的物种差异，以及 AHR 功能的细胞、组织和背景依赖性。该评论集中于 AHR 在能量消耗与微生物和非传染性炎症之间的整合中的作用，后者以肥胖介导的非酒精性脂肪性肝病为例。控制耗能性炎症的机制之一是信号小体，它参与视黄酸触发的中性粒细胞分化和 NADPH 氧化酶复合物 (NOX) 的调节。已建立的信号小体成分包括 AHR、CD38、多种蛋白激酶和衔接蛋白。为了预防慢性炎症性疾病，必须精确调节一系列炎症反应与能量消耗之间的复杂相互作用。要在感染中存活下来，既需要清除病原体，又需要防止组织受到炎症损伤。防御是耗能的合成代谢程序。因此，已经进化出通过代谢重编程使巨噬细胞产生抗炎、分解代谢耐受的程序。讨论了 AHR 激动剂治疗慢性炎症性疾病的选择。
