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Title: How Ah Receptor Ligand Specificity Became Important in Understanding Its Physiological Function.

Authors: Murray, Iain A; Perdew, Gary H

Published In Int J Mol Sci, (2020 Dec 17)

Abstract: Increasingly, the aryl hydrocarbon receptor (AHR) is being recognized as a sensor for endogenous and pseudo-endogenous metabolites, and in particular microbiota and host generated tryptophan metabolites. One proposed explanation for this is the role of the AHR in innate immune signaling within barrier tissues in response to the presence of microorganisms. A number of cytokine/chemokine genes exhibit a combinatorial increase in transcription upon toll-like receptors and AHR activation, supporting this concept. The AHR also plays a role in the enhanced differentiation of intestinal and dermal epithelium leading to improved barrier function. Importantly, from an evolutionary perspective many of these tryptophan metabolites exhibit greater activation potential for the human AHR when compared to the rodent AHR. These observations underscore the importance of the AHR in barrier tissues and may lead to pharmacologic therapeutic intervention.

PubMed ID: 33348604 Exiting the NIEHS site

MeSH Terms: Animals; Basic Helix-Loop-Helix Transcription Factors/agonists; Basic Helix-Loop-Helix Transcription Factors/antagonists & inhibitors; Basic Helix-Loop-Helix Transcription Factors/genetics; Basic Helix-Loop-Helix Transcription Factors/metabolism*; Cytochrome P-450 CYP1A1/metabolism; Cytokines/metabolism; Gastrointestinal Microbiome/physiology*; Humans; Ligands; Mice; Mice, Knockout; Receptors, Aryl Hydrocarbon/agonists; Receptors, Aryl Hydrocarbon/antagonists & inhibitors; Receptors, Aryl Hydrocarbon/genetics; Receptors, Aryl Hydrocarbon/metabolism*; Signal Transduction/physiology*; Tryptophan/metabolism

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