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AhR and IDO1 in pathogenesis of Covid-19 and the “Systemic AhR Activation Syndrome:” a translational review and therapeutic perspectives
Covid-19 is the acute illness caused by SARS-CoV-2 with initial clinical symptoms such as cough, fever, malaise, headache, and anosmia. After entry into cells, corona viruses (CoV) activate aryl hydrocarbon receptors (AhRs) by an indoleamine 2,3-dioxygenase (IDO1)-independent mechanism, bypassing th...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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IOS Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592680/ https://www.ncbi.nlm.nih.gov/pubmed/32597823 http://dx.doi.org/10.3233/RNN-201042 |
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author | Turski, Waldemar A. Wnorowski, Artur Turski, Gabrielle N. Turski, Christopher A. Turski, Lechoslaw |
author_facet | Turski, Waldemar A. Wnorowski, Artur Turski, Gabrielle N. Turski, Christopher A. Turski, Lechoslaw |
author_sort | Turski, Waldemar A. |
collection | PubMed |
description | Covid-19 is the acute illness caused by SARS-CoV-2 with initial clinical symptoms such as cough, fever, malaise, headache, and anosmia. After entry into cells, corona viruses (CoV) activate aryl hydrocarbon receptors (AhRs) by an indoleamine 2,3-dioxygenase (IDO1)-independent mechanism, bypassing the IDO1-kynurenine-AhR pathway. The IDO1-kynurenine-AhR signaling pathway is used by multiple viral, microbial and parasitic pathogens to activate AhRs and to establish infections. AhRs enhance their own activity through an IDO1-AhR-IDO1 positive feedback loop prolonging activation induced by pathogens. Direct activation of AhRs by CoV induces immediate and simultaneous up-regulation of diverse AhR-dependent downstream effectors, and this, in turn, results in a “Systemic AhR Activation Syndrome” (SAAS) consisting of inflammation, thromboembolism, and fibrosis, culminating in multiple organ injuries, and death. Activation of AhRs by CoV may lead to diverse sets of phenotypic disease pictures depending on time after infection, overall state of health, hormonal balance, age, gender, comorbidities, but also diet and environmental factors modulating AhRs. We hypothesize that elimination of factors known to up-regulate AhRs, or implementation of measures known to down-regulate AhRs, should decrease severity of infection. Although therapies selectively down-regulating both AhR and IDO1 are currently lacking, medications in clinical use such as dexamethasone may down-regulate both AhR and IDO1 genes, as calcitriol/vitamin D(3) may down-regulate the AhR gene, and tocopherol/vitamin E may down-regulate the IDO1 gene. Supplementation of calcitriol should therefore be subjected to epidemiological studies and tested in prospective trials for prevention of CoV infections, as should tocopherol, whereas dexamethasone could be tried in interventional trials. Because lack of physical exercise activates AhRs via the IDO1-kynurenine-AhR signaling pathway increasing risk of infection, physical exercise should be encouraged during quarantines and stay-at-home orders during pandemic outbreaks. Understanding which factors affect gene expression of both AhR and IDO1 may help in designing therapies to prevent and treat humans suffering from Covid-19. |
format | Online Article Text |
id | pubmed-7592680 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | IOS Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-75926802020-10-30 AhR and IDO1 in pathogenesis of Covid-19 and the “Systemic AhR Activation Syndrome:” a translational review and therapeutic perspectives Turski, Waldemar A. Wnorowski, Artur Turski, Gabrielle N. Turski, Christopher A. Turski, Lechoslaw Restor Neurol Neurosci Research Article Covid-19 is the acute illness caused by SARS-CoV-2 with initial clinical symptoms such as cough, fever, malaise, headache, and anosmia. After entry into cells, corona viruses (CoV) activate aryl hydrocarbon receptors (AhRs) by an indoleamine 2,3-dioxygenase (IDO1)-independent mechanism, bypassing the IDO1-kynurenine-AhR pathway. The IDO1-kynurenine-AhR signaling pathway is used by multiple viral, microbial and parasitic pathogens to activate AhRs and to establish infections. AhRs enhance their own activity through an IDO1-AhR-IDO1 positive feedback loop prolonging activation induced by pathogens. Direct activation of AhRs by CoV induces immediate and simultaneous up-regulation of diverse AhR-dependent downstream effectors, and this, in turn, results in a “Systemic AhR Activation Syndrome” (SAAS) consisting of inflammation, thromboembolism, and fibrosis, culminating in multiple organ injuries, and death. Activation of AhRs by CoV may lead to diverse sets of phenotypic disease pictures depending on time after infection, overall state of health, hormonal balance, age, gender, comorbidities, but also diet and environmental factors modulating AhRs. We hypothesize that elimination of factors known to up-regulate AhRs, or implementation of measures known to down-regulate AhRs, should decrease severity of infection. Although therapies selectively down-regulating both AhR and IDO1 are currently lacking, medications in clinical use such as dexamethasone may down-regulate both AhR and IDO1 genes, as calcitriol/vitamin D(3) may down-regulate the AhR gene, and tocopherol/vitamin E may down-regulate the IDO1 gene. Supplementation of calcitriol should therefore be subjected to epidemiological studies and tested in prospective trials for prevention of CoV infections, as should tocopherol, whereas dexamethasone could be tried in interventional trials. Because lack of physical exercise activates AhRs via the IDO1-kynurenine-AhR signaling pathway increasing risk of infection, physical exercise should be encouraged during quarantines and stay-at-home orders during pandemic outbreaks. Understanding which factors affect gene expression of both AhR and IDO1 may help in designing therapies to prevent and treat humans suffering from Covid-19. IOS Press 2020-09-24 /pmc/articles/PMC7592680/ /pubmed/32597823 http://dx.doi.org/10.3233/RNN-201042 Text en © 2020 – IOS Press and the authors. All rights reserved https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Turski, Waldemar A. Wnorowski, Artur Turski, Gabrielle N. Turski, Christopher A. Turski, Lechoslaw AhR and IDO1 in pathogenesis of Covid-19 and the “Systemic AhR Activation Syndrome:” a translational review and therapeutic perspectives |
title | AhR and IDO1 in pathogenesis of Covid-19 and the “Systemic AhR Activation Syndrome:” a translational review and therapeutic perspectives |
title_full | AhR and IDO1 in pathogenesis of Covid-19 and the “Systemic AhR Activation Syndrome:” a translational review and therapeutic perspectives |
title_fullStr | AhR and IDO1 in pathogenesis of Covid-19 and the “Systemic AhR Activation Syndrome:” a translational review and therapeutic perspectives |
title_full_unstemmed | AhR and IDO1 in pathogenesis of Covid-19 and the “Systemic AhR Activation Syndrome:” a translational review and therapeutic perspectives |
title_short | AhR and IDO1 in pathogenesis of Covid-19 and the “Systemic AhR Activation Syndrome:” a translational review and therapeutic perspectives |
title_sort | ahr and ido1 in pathogenesis of covid-19 and the “systemic ahr activation syndrome:” a translational review and therapeutic perspectives |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592680/ https://www.ncbi.nlm.nih.gov/pubmed/32597823 http://dx.doi.org/10.3233/RNN-201042 |
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