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Fighting the Fire: Mechanisms of Inflammatory Gene Regulation by the Glucocorticoid Receptor
For many decades, glucocorticoids have been widely used as the gold standard treatment for inflammatory conditions. Unfortunately, their clinical use is limited by severe adverse effects such as insulin resistance, cardiometabolic diseases, muscle and skin atrophies, osteoporosis, and depression. Gl...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6693390/ https://www.ncbi.nlm.nih.gov/pubmed/31440248 http://dx.doi.org/10.3389/fimmu.2019.01859 |
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author | Escoter-Torres, Laura Caratti, Giorgio Mechtidou, Aikaterini Tuckermann, Jan Uhlenhaut, Nina Henriette Vettorazzi, Sabine |
author_facet | Escoter-Torres, Laura Caratti, Giorgio Mechtidou, Aikaterini Tuckermann, Jan Uhlenhaut, Nina Henriette Vettorazzi, Sabine |
author_sort | Escoter-Torres, Laura |
collection | PubMed |
description | For many decades, glucocorticoids have been widely used as the gold standard treatment for inflammatory conditions. Unfortunately, their clinical use is limited by severe adverse effects such as insulin resistance, cardiometabolic diseases, muscle and skin atrophies, osteoporosis, and depression. Glucocorticoids exert their effects by binding to the Glucocorticoid Receptor (GR), a ligand-activated transcription factor which both positively, and negatively regulates gene expression. Extensive research during the past several years has uncovered novel mechanisms by which the GR activates and represses its target genes. Genome-wide studies and mouse models have provided valuable insight into the molecular mechanisms of inflammatory gene regulation by GR. This review focusses on newly identified target genes and GR co-regulators that are important for its anti-inflammatory effects in innate immune cells, as well as mutations within the GR itself that shed light on its transcriptional activity. This research progress will hopefully serve as the basis for the development of safer immune suppressants with reduced side effect profiles. |
format | Online Article Text |
id | pubmed-6693390 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-66933902019-08-22 Fighting the Fire: Mechanisms of Inflammatory Gene Regulation by the Glucocorticoid Receptor Escoter-Torres, Laura Caratti, Giorgio Mechtidou, Aikaterini Tuckermann, Jan Uhlenhaut, Nina Henriette Vettorazzi, Sabine Front Immunol Immunology For many decades, glucocorticoids have been widely used as the gold standard treatment for inflammatory conditions. Unfortunately, their clinical use is limited by severe adverse effects such as insulin resistance, cardiometabolic diseases, muscle and skin atrophies, osteoporosis, and depression. Glucocorticoids exert their effects by binding to the Glucocorticoid Receptor (GR), a ligand-activated transcription factor which both positively, and negatively regulates gene expression. Extensive research during the past several years has uncovered novel mechanisms by which the GR activates and represses its target genes. Genome-wide studies and mouse models have provided valuable insight into the molecular mechanisms of inflammatory gene regulation by GR. This review focusses on newly identified target genes and GR co-regulators that are important for its anti-inflammatory effects in innate immune cells, as well as mutations within the GR itself that shed light on its transcriptional activity. This research progress will hopefully serve as the basis for the development of safer immune suppressants with reduced side effect profiles. Frontiers Media S.A. 2019-08-07 /pmc/articles/PMC6693390/ /pubmed/31440248 http://dx.doi.org/10.3389/fimmu.2019.01859 Text en Copyright © 2019 Escoter-Torres, Caratti, Mechtidou, Tuckermann, Uhlenhaut and Vettorazzi. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Escoter-Torres, Laura Caratti, Giorgio Mechtidou, Aikaterini Tuckermann, Jan Uhlenhaut, Nina Henriette Vettorazzi, Sabine Fighting the Fire: Mechanisms of Inflammatory Gene Regulation by the Glucocorticoid Receptor |
title | Fighting the Fire: Mechanisms of Inflammatory Gene Regulation by the Glucocorticoid Receptor |
title_full | Fighting the Fire: Mechanisms of Inflammatory Gene Regulation by the Glucocorticoid Receptor |
title_fullStr | Fighting the Fire: Mechanisms of Inflammatory Gene Regulation by the Glucocorticoid Receptor |
title_full_unstemmed | Fighting the Fire: Mechanisms of Inflammatory Gene Regulation by the Glucocorticoid Receptor |
title_short | Fighting the Fire: Mechanisms of Inflammatory Gene Regulation by the Glucocorticoid Receptor |
title_sort | fighting the fire: mechanisms of inflammatory gene regulation by the glucocorticoid receptor |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6693390/ https://www.ncbi.nlm.nih.gov/pubmed/31440248 http://dx.doi.org/10.3389/fimmu.2019.01859 |
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