scholarly journals Species-Specific Differences in Aryl Hydrocarbon Receptor Responses: How and Why?

2021 ◽  
Vol 22 (24) ◽  
pp. 13293
Author(s):  
Xiaoting Xu ◽  
Xi Zhang ◽  
Yuzhu Yuan ◽  
Yongrui Zhao ◽  
Hamza M. Fares ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Species Differences ◽  
New Drugs ◽  
Environmental Toxicants ◽  
Molecular Configuration ◽  
Cis Acting ◽  
Toxicological Effects ◽  
Aryl Hydrocarbon ◽  
Wide Range ◽  
Species Specific

The aryl hydrocarbon receptor (AhR) is a transcription factor that regulates a wide range of biological and toxicological effects by binding to specific ligands. AhR ligands exist in various internal and external ecological systems, such as in a wide variety of hydrophobic environmental contaminants and naturally occurring chemicals. Most of these ligands have shown differential responses among different species. Understanding the differences and their mechanisms helps in designing better experimental animal models, improves our understanding of the environmental toxicants related to AhR, and helps to screen and develop new drugs. This review systematically discusses the species differences in AhR activation effects and their modes of action. We focus on the species differences following AhR activation from two aspects: (1) the molecular configuration and activation of AhR and (2) the contrast of cis-acting elements corresponding to AhR. The variations in the responses seen in humans and other species following the activation of the AhR signaling pathway can be attributed to both factors.

scholarly journals Diet–Host–Microbiota Interactions Shape Aryl Hydrocarbon Receptor Ligand Production to Modulate Intestinal Homeostasis

2021 ◽  
Vol 41 (1) ◽  
pp. 455-478
Author(s):  
Huajun Han ◽  
Stephen Safe ◽  
Arul Jayaraman ◽  
Robert S. Chapkin
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Environmental Toxicants ◽  
Cellular Functions ◽  
Developmental Defects ◽  
Helix Loop Helix ◽  
Aryl Hydrocarbon ◽  
Colon Tumorigenesis ◽  
Wide Range ◽  
Bowel Diseases ◽  
Context Specific

The aryl hydrocarbon receptor (AhR) is a ligand-activated basic-helix-loop-helix transcription factor that binds structurally diverse ligands and senses cues from environmental toxicants and physiologically relevant dietary/microbiota-derived ligands. The AhR is an ancient conserved protein and is widely expressed across different tissues in vertebrates and invertebrates. AhR signaling mediates a wide range of cellular functions in a ligand-, cell type–, species-, and context-specific manner. Dysregulation of AhR signaling is linked to many developmental defects and chronic diseases. In this review, we discuss the emerging role of AhR signaling in mediating bidirectional host–microbiome interactions. We also consider evidence showing the potential for the dietary/microbial enhancement ofhealth-promoting AhR ligands to improve clinical pathway management in the context of inflammatory bowel diseases and colon tumorigenesis.

Species differences in affinity of rat and human aryl hydrocarbon receptor for ligands

Toxicology ◽  
2008 ◽  
Vol 253 (1-3) ◽  
pp. 23
Author(s):  
Ming Qi Fan ◽  
Tao Jiang ◽  
David R. Bell
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Species Differences ◽  
Aryl Hydrocarbon

Suppression of adipocyte differentiation by Cordyceps militaris through activation of the aryl hydrocarbon receptor

2008 ◽  
Vol 295 (4) ◽  
pp. E859-E867 ◽  
Author(s):  
Tsuyoshi Shimada ◽  
Nobuhiko Hiramatsu ◽  
Ayumi Kasai ◽  
Mai Mukai ◽  
Maro Okamura ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Mammalian Cells ◽  
Adipocyte Differentiation ◽  
Biological Activities ◽  
Cordyceps Militaris ◽  
Dominant Negative ◽  
Peroxisome Proliferator ◽  
Monocyte Chemoattractant Protein 1 ◽  
Aryl Hydrocarbon ◽  
Wide Range

Mycelial extracts have a wide range of biological activities that modulate functions of mammalian cells. In this report, we sought to identify antiadipogenic mycelia with the use of 3T3-L1 cells and found that the extract of Cordyceps militaris exclusively suppressed differentiation of 3T3-L1 preadipocytes into mature adipocytes without affecting cell viability. This inhibitory effect was dose dependent, reversible, and associated with 1) a decrease in lipid accumulation, 2) blunted induction of adipocyte markers including adiponectin, peroxisome proliferator-activated receptor-γ, and CCAAT/enhancer binding protein-α, and 3) sustained expression of a preadipocyte marker, monocyte chemoattractant protein-1. C. militaris also significantly decreased accumulation of lipid and hypertrophy in mature adipocytes and preserved their response to insulin (phosphorylation of Akt) during prolonged culture. Subsequent experiments revealed that C. militaris has the potential to activate the aryl hydrocarbon receptor (AhR). In 3T3-L1 cells, treatment with AhR agonists including benzo[ a]pyrene and 3-methylcholanthrene reproduced the antiadipogenic effect of C. militaris. Furthermore, dominant-negative inhibition of AhR abrogated the suppressive effect of C. militaris on adipocyte differentiation. These results suggest that C. militaris has the potential to interfere with adipocyte differentiation through activation of AhR.

scholarly journals Hypersensitivity of Aryl Hydrocarbon Receptor-Deficient Mice to Lipopolysaccharide-Induced Septic Shock

2009 ◽  
Vol 29 (24) ◽  
pp. 6391-6400 ◽  
Author(s):  
Hiroki Sekine ◽  
Junsei Mimura ◽  
Motohiko Oshima ◽  
Hiromi Okawa ◽  
Jun Kanno ◽  
...  
Keyword(s):  
Septic Shock ◽  
Aryl Hydrocarbon Receptor ◽  
Plasminogen Activator Inhibitor ◽  
Dependent Manner ◽  
Wild Type ◽  
Toxicological Effects ◽  
Aryl Hydrocarbon ◽  
Polycyclic Aromatic ◽  
Deficient Mice ◽  
Activator Inhibitor

ABSTRACT Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, is known to mediate a wide variety of pharmacological and toxicological effects caused by polycyclic aromatic hydrocarbons. Recent studies have revealed that AhR is involved in the normal development and homeostasis of many organs. Here, we demonstrate that AhR knockout (AhR KO) mice are hypersensitive to lipopolysaccharide (LPS)-induced septic shock, mainly due to the dysfunction of their macrophages. In response to LPS, bone marrow-derived macrophages (BMDM) of AhR KO mice secreted an enhanced amount of interleukin-1β (IL-1β). Since the enhanced IL-1β secretion was suppressed by supplementing Plasminogen activator inhibitor-2 (Pai-2) expression through transduction with Pai-2-expressing adenoviruses, reduced Pai-2 expression could be a cause of the increased IL-1β secretion by AhR KO mouse BMDM. Analysis of gene expression revealed that AhR directly regulates the expression of Pai-2 through a mechanism involving NF-κB but not AhR nuclear translocator (Arnt), in an LPS-dependent manner. Together with the result that administration of the AhR ligand 3-methylcholanthrene partially protected mice with wild-type AhR from endotoxin-induced death, these results raise the possibility that an appropriate AhR ligand may be useful for treating patients with inflammatory disorders.

scholarly journals The Aryl Hydrocarbon Receptor and the Maintenance of Lung Health

2018 ◽  
Vol 19 (12) ◽  
pp. 3882 ◽  
Author(s):  
Necola Guerrina ◽  
Hussein Traboulsi ◽  
David Eidelman ◽  
Carolyn Baglole
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Cigarette Smoke ◽  
Respiratory Illness ◽  
Chronic Obstructive ◽  
Environmental Toxicants ◽  
Obstructive Pulmonary Disease ◽  
Aryl Hydrocarbon ◽  
Disease States ◽  
Physiological Processes ◽  
Lung Health

Much of what is known about the Aryl Hydrocarbon Receptor (AhR) centers on its ability to mediate the deleterious effects of the environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin). However, the AhR is both ubiquitously-expressed and evolutionarily-conserved, suggesting that it evolved for purposes beyond strictly mediating responses to man-made environmental toxicants. There is growing evidence that the AhR is required for the maintenance of health, as it is implicated in physiological processes such as xenobiotic metabolism, organ development and immunity. Dysregulation of AhR expression and activity is also associated with a variety of disease states, particularly those at barrier organs such as the skin, gut and lungs. The lungs are particularly vulnerable to inhaled toxicants such as cigarette smoke. However, the role of the AhR in diseases such as chronic obstructive pulmonary disease (COPD)—a respiratory illness caused predominately by cigarette smoking—and lung cancer remains largely unexplored. This review will discuss the growing body of literature that provides evidence that the AhR protects the lungs against the damaging effects of cigarette smoke.

scholarly journals Environmental Toxicants May Modulate Osteoblast Differentiation by a Mechanism Involving the Aryl Hydrocarbon Receptor

2007 ◽  
Vol 22 (10) ◽  
pp. 1571-1580 ◽  
Author(s):  
Elizabeth P Ryan ◽  
Jonathan D Holz ◽  
Mary Mulcahey ◽  
Tzong-jen Sheu ◽  
Thomas A Gasiewicz ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Osteoblast Differentiation ◽  
Environmental Toxicants ◽  
Aryl Hydrocarbon

scholarly journals The Aryl Hydrocarbon Receptor as a Modulator of Anti-viral Immunity

2021 ◽  
Vol 12 ◽  
Author(s):  
Maria Florencia Torti ◽  
Federico Giovannoni ◽  
Francisco Javier Quintana ◽  
Cybele Carina García
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Target Genes ◽  
Environmental Pollutants ◽  
Adaptive Immune Response ◽  
Viral Immunity ◽  
Adaptive Immune ◽  
Aryl Hydrocarbon ◽  
Wide Range ◽  
Tryptophan Metabolites ◽  
Exogenous Origin

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, which interacts with a wide range of organic molecules of endogenous and exogenous origin, including environmental pollutants, tryptophan metabolites, and microbial metabolites. The activation of AHR by these agonists drives its translocation into the nucleus where it controls the expression of a large number of target genes that include the AHR repressor (AHRR), detoxifying monooxygenases (CYP1A1 and CYP1B1), and cytokines. Recent advances reveal that AHR signaling modulates aspects of the intrinsic, innate and adaptive immune response to diverse microorganisms. This review will focus on the increasing evidence supporting a role for AHR as a modulator of the host response to viral infection.

Sign in / Sign up

Export Citation Format

Share Document