Original article by Indigo Biosciences
Our partner INDIGO Biosciences offers a Human Aryl Hydrocarbon Receptor (AhR) assay kit as an all-inclusive luciferase reporter system that includes, in addition to AhR Reporter Cells, two optimized media for use during cell culture and in diluting the user’s test samples, a reference agonist, Luciferase Detection Reagent, and a cell culture-ready assay plate. In this blog post, you will learn more about the function of AhR and its role in various diseases.
These topics await you:
1) What is the Aryl Hydrocarbon Receptor?
3) The pharmaceutical industry's interest in AhR
4) INDIGO Biosciences: Experts for in vitro toxicology and nuclear receptors
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What is the Aryl Hydrocarbon Receptor?
The Aryl Hydrocarbon Receptor (AhR) is a ligand-activated transcription factor protein that belongs to the basic helix-loop-helix (bHLH) Per-Arnt-Sim (PAS) family of transcription factors. It was originally characterized as the dioxin or polycyclic aromatic hydrocarbon receptor due to the role it plays in detoxifying a variety of environmental pollutants. That was until extensive research identified several groups of endogenous ligands and AhR’s function in biological development and homeostasis was discovered. This intracellular receptor is widely expressed in human tissues and has diverse physiological roles, including the regulation of immune system development, cell proliferation, and differentiation.
AhR merges microbial and environmental signals to control transcriptional programs in a cell-type-specific, ligand-specific, and context-specific manner. When activated, AhR forms a complex with another protein, ARNT, and translocates into the nucleus where it binds to specific DNA sequences, resulting in the activation or inhibition of target genes.
AhR’s Role in Disease
The importance of AhR and its signaling in toxicology, immune function and disease is continuing to be uncovered. AhR is activated by numerous endogenous ligands and exogenous compounds and is an essential transcriptional component of the body’s response to environmental stressors. AhR plays a critical role in detoxifying environmental pollutants and other exogenous compounds by controlling the expression of a battery of genes. The activation of AhR by environmental toxins has been linked to adverse health outcomes including immunosuppression, reproductive dysfunction, cancer, and developmental defects.
Research has recognized that the activation of AhR by certain endogenous compounds such as tryptophan metabolites is connected to the regulation of immune system function. This implicates the dysregulations of AhR to several autoimmune diseases as well as complications caused by immunosuppression. AhR has also been considered a new focus in cardiovascular disease. While it was recently discovered that AhR function is closely associated with the development of atherosclerosis, the roles of AhR in the pathological development of atherosclerosis and atherosclerosis‑associated diseases is still undetermined. AhR is also expressed in many ocular tissues including the retina, choroid, cornea, and the orbit. AhR, and it has been identified to have a significant role in age-related macular degeneration (AMD), autoimmune uveitis, and other ocular diseases.
The pharmaceutical industry's interest in AhR
AhR’s ability to respond to both endogenous and exogenous compounds and being expressed in many human tissues makes it a crucial target for drug discovery and development. There are numerous synthetic and natural compounds that activate or inhibit AhR that are currently being developed and tested as potential drug candidates. Additionally, AhR’s critical role in responding to environmental stressors has created significant interest in developing AhR-targeted drugs for several clinical applications, including cancer, inflammatory diseases, and metabolic disorders.
A drug targeting AhR for its role in immune system functioning is Benvitimod. It is a small molecule AhR agonist, which was approved in May of 2022, and is considered a first in its class medication for the treatment of psoriasis. There are also selective AhR antagonists being investigated for treatment of autoimmune diseases like rheumatoid arthritis and lupus. Development of AhR-targeted drugs is an active area of research and holds promise for the treatment of various diseases.
INDIGO Biosciences: Experts for in vitro toxicology and nuclear receptors
INDIGO’s cell-based reporter assays allow scientists to detect any biological activity that their test samples may exert against a specific receptor present in the cell. They utilize firefly luciferase reporter gene technology which provides superior precision and sensitivity. Since the receptor binding controls the expression of the luciferase reporter gene, luciferase activity in the cells can be correlated directly with the activity of the receptor. The strength of an interaction of a chemical with the target receptor is quantified using a luminometer to measure the level of light emitted. Contact us today to learn more about AhR and all of INDIGO’s other assay kits!
