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Epidermal growth factor-mediated activation of the unliganded glucocorticoid receptor in A549 cells
Multiple studies have described ligand-independent glucocorticoid receptor (GR) activation in which non-steroidal ligands are able to activate the GR in the absence of glucocorticoids. This study investigates the regulatory effects of epidermal growth factor (EGF) on cytokine gene expression in orde...
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| Format: | Thesis |
| Language: | English English |
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Department of Molecular and Cell Biology
2025
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| _version_ | 1867613271600660480 |
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| access_status_str | Open Access |
| author | Kemp, Calvin |
| author2 | Hapgood, Janet |
| author_browse | Hapgood, Janet Kemp, Calvin |
| author_facet | Hapgood, Janet Kemp, Calvin |
| author_sort | Kemp, Calvin |
| collection | Thesis |
| description | Multiple studies have described ligand-independent glucocorticoid receptor (GR) activation in which non-steroidal ligands are able to activate the GR in the absence of glucocorticoids. This study investigates the regulatory effects of epidermal growth factor (EGF) on cytokine gene expression in order to determine whether previously published examples of EGF repressing the expression of interleukin 6 (IL-6) mRNA occur in other cell types and whether the effects of EGF are mediated via the GR. This study provides the first evidence of a single ligand (EGF) causing ligand-independent GR activation, resulting in the regulation of cytokine genes in the lung epithelium fibroblast A549 cell line. Evidence suggests that the EGF-induced repression acts on signalling via the TLR-2 receptor but not via the protein kinase C (PKC) pathway. The EGF response is shown to act via the nuclear factor kappa B (NF-κB) promoter element in a GR-dependent manner. Some mechanistic insights into the regulation are provided by demonstrating that EGF results in site-specific GR phosphorylation, while EGF does not induce GR turnover or alter GR protein expression levels. A novel finding is that regulation of IL-6 mRNA expression is shown to require protein translation. Taken together, this study provides evidence that expands on the knowledge of how EGF may affect immune function and provides proof of the mechanisms likely involved. |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/41652 |
| institution | University of Cape Town (South Africa) |
| language | English eng |
| last_indexed | 2026-06-10T12:33:28.738Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2025 |
| publishDateRange | 2025 |
| publishDateSort | 2025 |
| publisher | Department of Molecular and Cell Biology |
| publisherStr | Department of Molecular and Cell Biology |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/41652 Epidermal growth factor-mediated activation of the unliganded glucocorticoid receptor in A549 cells Kemp, Calvin Hapgood, Janet Avenant, Chanel Epidermal A549 cells Multiple studies have described ligand-independent glucocorticoid receptor (GR) activation in which non-steroidal ligands are able to activate the GR in the absence of glucocorticoids. This study investigates the regulatory effects of epidermal growth factor (EGF) on cytokine gene expression in order to determine whether previously published examples of EGF repressing the expression of interleukin 6 (IL-6) mRNA occur in other cell types and whether the effects of EGF are mediated via the GR. This study provides the first evidence of a single ligand (EGF) causing ligand-independent GR activation, resulting in the regulation of cytokine genes in the lung epithelium fibroblast A549 cell line. Evidence suggests that the EGF-induced repression acts on signalling via the TLR-2 receptor but not via the protein kinase C (PKC) pathway. The EGF response is shown to act via the nuclear factor kappa B (NF-κB) promoter element in a GR-dependent manner. Some mechanistic insights into the regulation are provided by demonstrating that EGF results in site-specific GR phosphorylation, while EGF does not induce GR turnover or alter GR protein expression levels. A novel finding is that regulation of IL-6 mRNA expression is shown to require protein translation. Taken together, this study provides evidence that expands on the knowledge of how EGF may affect immune function and provides proof of the mechanisms likely involved. 2025-08-29T12:42:09Z 2025-08-29T12:42:09Z 2025 2025-08-29T12:35:14Z Thesis / Dissertation Masters MSc http://hdl.handle.net/11427/41652 en eng application/pdf Department of Molecular and Cell Biology Faculty of Science University of Cape Town |
| spellingShingle | Epidermal A549 cells Kemp, Calvin Epidermal growth factor-mediated activation of the unliganded glucocorticoid receptor in A549 cells |
| thesis_degree_str | Master's |
| title | Epidermal growth factor-mediated activation of the unliganded glucocorticoid receptor in A549 cells |
| title_full | Epidermal growth factor-mediated activation of the unliganded glucocorticoid receptor in A549 cells |
| title_fullStr | Epidermal growth factor-mediated activation of the unliganded glucocorticoid receptor in A549 cells |
| title_full_unstemmed | Epidermal growth factor-mediated activation of the unliganded glucocorticoid receptor in A549 cells |
| title_short | Epidermal growth factor-mediated activation of the unliganded glucocorticoid receptor in A549 cells |
| title_sort | epidermal growth factor mediated activation of the unliganded glucocorticoid receptor in a549 cells |
| topic | Epidermal A549 cells |
| url | http://hdl.handle.net/11427/41652 |
| work_keys_str_mv | AT kempcalvin epidermalgrowthfactormediatedactivationoftheunligandedglucocorticoidreceptorina549cells |