Functional cross-talk among cytokines, T-cell receptor, and glucocorticoid receptor transcriptional activity and action
The main communicators between the neuroendocrine and immune systems are cytokines and hormones. We studied the molecular interaction between immune activators (cytokines and T-cell receptors [TCRs]) and the glucocorticoid receptor (GR) in cells in which glucocorticoids play a key regulatory functio...
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00778923_v917_n_p672_Arzt http://hdl.handle.net/20.500.12110/paper_00778923_v917_n_p672_Arzt |
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paper:paper_00778923_v917_n_p672_Arzt2023-06-08T15:07:35Z Functional cross-talk among cytokines, T-cell receptor, and glucocorticoid receptor transcriptional activity and action Kovalovsky, Damián Muller Igaz, Lionel Costas, Mónica Alejandra Plazas, Paola Viviana Refojo, Damián Páez Pereda, Marcelo cytokine glucocorticoid glucocorticoid receptor immunoglobulin enhancer binding protein interleukin 1 T lymphocyte receptor tumor necrosis factor tumor necrosis factor alpha apoptosis conference paper cytotoxicity genetic transcription genetic transfection human hypophysis immune system molecular interaction neuroendocrine system nonhuman protein expression receptor upregulation signal transduction The main communicators between the neuroendocrine and immune systems are cytokines and hormones. We studied the molecular interaction between immune activators (cytokines and T-cell receptors [TCRs]) and the glucocorticoid receptor (GR) in cells in which glucocorticoids play a key regulatory function: (1) cellular targets of TNF-induced cytotoxicity; (2) the pituitary gland; and (3) thymic cells. Cytokines (TNF-alpha and IL-1) increase glucocorticoid-induced transcriptional activity of the GR via the DNA-glucocorticoid response elements (GREs) in cells transfected with a glucocorticoid-inducible reporter plasmid. As a functional physiological correlate, priming of fibroblastic cells with a low dose of TNF significantly increases the sensitivity to glucocorticoid inhibition of TNF-induced apoptosis (without involving NF-κB). Priming of AtT-20 mouse corticotrophs and Cushing pituitary cells with IL-1 increases the sensitivity to glucocorticoid inhibition of CRH-induced ACTH/POMC expression. In thymocytes, activation of the T-cell receptor counteracts the glucocorticoid-induced thymic apoptosis by downregulating the glucocorticoid action on GRE-driven apoptotic genes. Thus, cytokines and immune mediators prevent their own deleterious effects not only by stimulating glucocorticoid production, but also by modifying the sensitivity of the target cells for the glucocorticoid counter-regulatory action. The functional cross-talk at the molecular level between immune signals and glucocorticoids is essential to determine the biological response to both mediators and constitutes the ultimate level of interaction between the immune and neuroendocrine mediators. Fil:Kovalovsky, D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Müller Igaz, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Costas, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Plazas, P. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Refojo, D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Páez-Pereda, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2000 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00778923_v917_n_p672_Arzt http://hdl.handle.net/20.500.12110/paper_00778923_v917_n_p672_Arzt |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
cytokine glucocorticoid glucocorticoid receptor immunoglobulin enhancer binding protein interleukin 1 T lymphocyte receptor tumor necrosis factor tumor necrosis factor alpha apoptosis conference paper cytotoxicity genetic transcription genetic transfection human hypophysis immune system molecular interaction neuroendocrine system nonhuman protein expression receptor upregulation signal transduction |
| spellingShingle |
cytokine glucocorticoid glucocorticoid receptor immunoglobulin enhancer binding protein interleukin 1 T lymphocyte receptor tumor necrosis factor tumor necrosis factor alpha apoptosis conference paper cytotoxicity genetic transcription genetic transfection human hypophysis immune system molecular interaction neuroendocrine system nonhuman protein expression receptor upregulation signal transduction Kovalovsky, Damián Muller Igaz, Lionel Costas, Mónica Alejandra Plazas, Paola Viviana Refojo, Damián Páez Pereda, Marcelo Functional cross-talk among cytokines, T-cell receptor, and glucocorticoid receptor transcriptional activity and action |
| topic_facet |
cytokine glucocorticoid glucocorticoid receptor immunoglobulin enhancer binding protein interleukin 1 T lymphocyte receptor tumor necrosis factor tumor necrosis factor alpha apoptosis conference paper cytotoxicity genetic transcription genetic transfection human hypophysis immune system molecular interaction neuroendocrine system nonhuman protein expression receptor upregulation signal transduction |
| description |
The main communicators between the neuroendocrine and immune systems are cytokines and hormones. We studied the molecular interaction between immune activators (cytokines and T-cell receptors [TCRs]) and the glucocorticoid receptor (GR) in cells in which glucocorticoids play a key regulatory function: (1) cellular targets of TNF-induced cytotoxicity; (2) the pituitary gland; and (3) thymic cells. Cytokines (TNF-alpha and IL-1) increase glucocorticoid-induced transcriptional activity of the GR via the DNA-glucocorticoid response elements (GREs) in cells transfected with a glucocorticoid-inducible reporter plasmid. As a functional physiological correlate, priming of fibroblastic cells with a low dose of TNF significantly increases the sensitivity to glucocorticoid inhibition of TNF-induced apoptosis (without involving NF-κB). Priming of AtT-20 mouse corticotrophs and Cushing pituitary cells with IL-1 increases the sensitivity to glucocorticoid inhibition of CRH-induced ACTH/POMC expression. In thymocytes, activation of the T-cell receptor counteracts the glucocorticoid-induced thymic apoptosis by downregulating the glucocorticoid action on GRE-driven apoptotic genes. Thus, cytokines and immune mediators prevent their own deleterious effects not only by stimulating glucocorticoid production, but also by modifying the sensitivity of the target cells for the glucocorticoid counter-regulatory action. The functional cross-talk at the molecular level between immune signals and glucocorticoids is essential to determine the biological response to both mediators and constitutes the ultimate level of interaction between the immune and neuroendocrine mediators. |
| author |
Kovalovsky, Damián Muller Igaz, Lionel Costas, Mónica Alejandra Plazas, Paola Viviana Refojo, Damián Páez Pereda, Marcelo |
| author_facet |
Kovalovsky, Damián Muller Igaz, Lionel Costas, Mónica Alejandra Plazas, Paola Viviana Refojo, Damián Páez Pereda, Marcelo |
| author_sort |
Kovalovsky, Damián |
| title |
Functional cross-talk among cytokines, T-cell receptor, and glucocorticoid receptor transcriptional activity and action |
| title_short |
Functional cross-talk among cytokines, T-cell receptor, and glucocorticoid receptor transcriptional activity and action |
| title_full |
Functional cross-talk among cytokines, T-cell receptor, and glucocorticoid receptor transcriptional activity and action |
| title_fullStr |
Functional cross-talk among cytokines, T-cell receptor, and glucocorticoid receptor transcriptional activity and action |
| title_full_unstemmed |
Functional cross-talk among cytokines, T-cell receptor, and glucocorticoid receptor transcriptional activity and action |
| title_sort |
functional cross-talk among cytokines, t-cell receptor, and glucocorticoid receptor transcriptional activity and action |
| publishDate |
2000 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00778923_v917_n_p672_Arzt http://hdl.handle.net/20.500.12110/paper_00778923_v917_n_p672_Arzt |
| work_keys_str_mv |
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| _version_ |
1768541698721316864 |