scholarly journals The Aryl Hydrocarbon Receptor in Energy Balance: The Road from Dioxin-Induced Wasting Syndrome to Combating Obesity with Ahr Ligands

2020 ◽  
Vol 22 (1) ◽  
pp. 49
Author(s):  
Nathaniel G. Girer ◽  
Craig R. Tomlinson ◽  
Cornelis J. Elferink
Keyword(s):  
Energy Metabolism ◽  
Aryl Hydrocarbon Receptor ◽  
Therapeutic Target ◽  
Reproductive Organs ◽  
Potential Therapeutic Target ◽  
The Road ◽  
Aryl Hydrocarbon ◽  
Wasting Syndrome ◽  
Toxicological Studies

The aryl hydrocarbon receptor (AHR) has been studied for over 40 years, yet our understanding of this ligand-activated transcription factor remains incomplete. Each year, novel findings continually force us to rethink the role of the AHR in mammalian biology. The AHR has historically been studied within the context of potent activation via AHR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), with a focus on how the AHR mediates TCDD toxicity. Research has subsequently revealed that the AHR is actively involved in distinct physiological processes ranging from the development of the liver and reproductive organs, to immune system function and wound healing. More recently, the AHR was implicated in the regulation of energy metabolism and is currently being investigated as a potential therapeutic target for obesity. In this review, we re-trace the steps through which the early toxicological studies of TCDD led to the conceptual framework for the AHR as a potential therapeutic target in metabolic disease. We additionally discuss the key discoveries that have been made concerning the role of the AHR in energy metabolism, as well as the current and future directions of the field.

scholarly journals A Protective Role of Aryl Hydrocarbon Receptor Repressor in Inflammation and Tumor Growth

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 589 ◽  
Author(s):  
Christoph F. A. Vogel ◽  
Yasuhiro Ishihara ◽  
Claire E. Campbell ◽  
Sarah Y. Kado ◽  
Aimy Nguyen-Chi ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Aryl Hydrocarbon Receptor ◽  
Inflammatory Responses ◽  
Environmental Pollutants ◽  
Protective Role ◽  
Potential Therapeutic Target ◽  
Embryonic Fibroblasts ◽  
Aryl Hydrocarbon ◽  
Enhancer Binding Protein

The aryl hydrocarbon receptor (AhR) is known for mediating the toxicity of environmental pollutants such as dioxins and numerous dioxin-like compounds, and is associated with the promotion of various malignancies, including lymphoma. The aryl hydrocarbon receptor repressor (AhRR), a ligand-independent, transcriptionally inactive AhR-like protein is known to repress AhR signaling through its ability to compete with the AhR for dimerization with the AhR nuclear translocator (ARNT). While AhRR effectively blocks AhR signaling, several aspects of the mechanism of AhRR’s functions are poorly understood, including suppression of inflammatory responses and its putative role as a tumor suppressor. In a transgenic mouse that overexpresses AhRR (AhRR Tg) we discovered that these mice suppress 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)- and inflammation-induced tumor growth after subcutaneous challenge of EL4 lymphoma cells. Using mouse embryonic fibroblasts (MEF) we found that AhRR overexpression suppresses the AhR-mediated anti-apoptotic response. The AhRR-mediated inhibition of apoptotic resistance was associated with a suppressed expression of interleukin (IL)-1β and cyclooxygenase (COX)-2, which was dependent on activation of protein kinase A (PKA) and the CAAT-enhancer-binding protein beta (C/EBPβ). These results provide mechanistic insights into the role of the AhRR to suppress inflammation and highlight the AhRR as a potential therapeutic target to suppress tumor growth.

scholarly journals The Role of Aryl Hydrocarbon Receptor (AhR) in Brain Tumors

2020 ◽  
Vol 21 (8) ◽  
pp. 2863 ◽  
Author(s):  
Maria L. Perepechaeva ◽  
Alevtina Y. Grishanova
Keyword(s):  
Brain Tumors ◽  
Aryl Hydrocarbon Receptor ◽  
Therapeutic Target ◽  
Current Knowledge ◽  
Cell Types ◽  
Pathological Process ◽  
Aryl Hydrocarbon ◽  
Oncogenic Protein ◽  
Different Cell Types

Primary brain tumors, both malignant and benign, are diagnosed in adults at an incidence rate of approximately 23 people per 100 thousand. The role of AhR in carcinogenesis has been a subject of debate, given that this protein may act as either an oncogenic protein or a tumor suppressor in different cell types and contexts. Lately, there is growing evidence that aryl hydrocarbon receptor (AhR) plays an important part in the development of brain tumors. The role of AhR in brain tumors is complicated, depending on the type of tumor, on ligands that activate AhR, and other features of the pathological process. In this review, we summarize current knowledge about AhR in relation to brain tumors and provide an overview of AhR’s potential as a therapeutic target.

scholarly journals The aryl hydrocarbon receptor and the gut–brain axis

2021 ◽  
Author(s):  
Andreia Barroso ◽  
João Vitor Mahler ◽  
Pedro Henrique Fonseca-Castro ◽  
Francisco J. Quintana
Keyword(s):  
Transcription Factor ◽  
Aryl Hydrocarbon Receptor ◽  
Therapeutic Target ◽  
Potential Value ◽  
Aryl Hydrocarbon ◽  
Immune Mediated ◽  
Health And Disease

AbstractThe aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor initially identified as the receptor for dioxin. Almost half a century after its discovery, AHR is now recognized as a receptor for multiple physiological ligands, with important roles in health and disease. In this review, we discuss the role of AHR in the gut–brain axis and its potential value as a therapeutic target for immune-mediated diseases.

scholarly journals The aryl hydrocarbon receptor in liver inflammation

2021 ◽  
Author(s):  
Antonella Carambia ◽  
Fenja Amrei Schuran
Keyword(s):  
Liver Disease ◽  
Immune Responses ◽  
Aryl Hydrocarbon Receptor ◽  
Current Knowledge ◽  
Regulatory Factor ◽  
Potential Therapeutic Target ◽  
Adaptive Immune ◽  
Aryl Hydrocarbon ◽  
Healthy Liver

AbstractThe aryl hydrocarbon receptor (AHR) is a ubiquitously expressed ligand-activated transcription factor with multifaceted physiological functions. In the immune system, AHR has been unequivocally identified as a key regulatory factor that can integrate environmental, dietary, or microbial signals into innate and adaptive immune responses. Correspondingly, AHR activity seems to be most important at barrier organs, such as the gut, skin, and lung. The liver is likewise prominently exposed to gut-derived dietary or microbial AHR ligands and, moreover, generates plenty of AHR ligands itself. Yet, surprisingly little is known about the role of AHR in the regulation of hepatic immune responses, which are normally biased towards tolerance, preventing harmful inflammation in response to innocuous stimuli. In this review, we summarize the current knowledge about the role of AHR in hepatic immune responses in the healthy liver as well as in inflammatory liver disease. Moreover, we discuss AHR as a potential therapeutic target in hepatic disorders, including autoimmune liver disease, liver fibrosis, and liver cancer.

Role of the Aryl Hydrocarbon Receptor (AhR) in Mediating the Effects of Coffee in the Colon

2021 ◽  
pp. 2100539
Author(s):  
Robert S. Chapkin ◽  
Laurie A. Davidson ◽  
Hyejin Park ◽  
Un‐Ho Jin ◽  
Yang‐Yi Fan ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Aryl Hydrocarbon

Role of the Aryl Hydrocarbon Receptor in the Pathogenesis of Chronic Rhinosinusitis with Nasal Polyps

Inflammation ◽  
2013 ◽  
Vol 37 (2) ◽  
pp. 387-395 ◽  
Author(s):  
Ping Wei ◽  
Guo-hua Hu ◽  
Hou-yong Kang ◽  
Hong-bing Yao ◽  
Wei Kou ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Aryl Hydrocarbon
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