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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.01859/full |
| _version_ | 1818777592021385216 |
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| author | Laura Escoter-Torres Giorgio Caratti Aikaterini Mechtidou Jan Tuckermann Nina Henriette Uhlenhaut Nina Henriette Uhlenhaut Sabine Vettorazzi |
| author_facet | Laura Escoter-Torres Giorgio Caratti Aikaterini Mechtidou Jan Tuckermann Nina Henriette Uhlenhaut Nina Henriette Uhlenhaut Sabine Vettorazzi |
| author_sort | Laura Escoter-Torres |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-18T11:31:16Z |
| format | Article |
| id | doaj.art-88d160c560264f77b94eabe21f0997e1 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-18T11:31:16Z |
| publishDate | 2019-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-88d160c560264f77b94eabe21f0997e12022-12-21T21:09:36ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-08-011010.3389/fimmu.2019.01859472478Fighting the Fire: Mechanisms of Inflammatory Gene Regulation by the Glucocorticoid ReceptorLaura Escoter-Torres0Giorgio Caratti1Aikaterini Mechtidou2Jan Tuckermann3Nina Henriette Uhlenhaut4Nina Henriette Uhlenhaut5Sabine Vettorazzi6Molecular Endocrinology, Helmholtz Zentrum München (HMGU), German Center for Diabetes Research (DZD), Institute for Diabetes and Cancer IDC, Munich, GermanyDepartment of Biology, Institute for Comparative Molecular Endocrinology, University of Ulm, Ulm, GermanyMolecular Endocrinology, Helmholtz Zentrum München (HMGU), German Center for Diabetes Research (DZD), Institute for Diabetes and Cancer IDC, Munich, GermanyDepartment of Biology, Institute for Comparative Molecular Endocrinology, University of Ulm, Ulm, GermanyMolecular Endocrinology, Helmholtz Zentrum München (HMGU), German Center for Diabetes Research (DZD), Institute for Diabetes and Cancer IDC, Munich, GermanyGene Center, Ludwig-Maximilians-Universität (LMU), Munich, GermanyDepartment of Biology, Institute for Comparative Molecular Endocrinology, University of Ulm, Ulm, GermanyFor 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.https://www.frontiersin.org/article/10.3389/fimmu.2019.01859/fullglucocorticoid receptorinflammationmacrophagesmouse modelsgene regulation |
| spellingShingle | Laura Escoter-Torres Giorgio Caratti Aikaterini Mechtidou Jan Tuckermann Nina Henriette Uhlenhaut Nina Henriette Uhlenhaut Sabine Vettorazzi Fighting the Fire: Mechanisms of Inflammatory Gene Regulation by the Glucocorticoid Receptor Frontiers in Immunology glucocorticoid receptor inflammation macrophages mouse models gene regulation |
| 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 | glucocorticoid receptor inflammation macrophages mouse models gene regulation |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.01859/full |
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