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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Autores principales: Arzt, E., Kovalovsky, D., Müller Igaz, L., Costas, M., Plazas, P., Refojo, D., Páez-Pereda, M., Reul, J.M.H.M., Stalla, G., Holsboer, F.
Formato: SER
Materias:
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
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_00778923_v917_n_p672_Arzt
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
id todo:paper_00778923_v917_n_p672_Arzt
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spelling todo:paper_00778923_v917_n_p672_Arzt2023-10-03T14:54:24Z Functional cross-talk among cytokines, T-cell receptor, and glucocorticoid receptor transcriptional activity and action Arzt, E. Kovalovsky, D. Müller Igaz, L. Costas, M. Plazas, P. Refojo, D. Páez-Pereda, M. Reul, J.M.H.M. Stalla, G. Holsboer, F. 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. SER info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar 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
Arzt, E.
Kovalovsky, D.
Müller Igaz, L.
Costas, M.
Plazas, P.
Refojo, D.
Páez-Pereda, M.
Reul, J.M.H.M.
Stalla, G.
Holsboer, F.
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.
format SER
author Arzt, E.
Kovalovsky, D.
Müller Igaz, L.
Costas, M.
Plazas, P.
Refojo, D.
Páez-Pereda, M.
Reul, J.M.H.M.
Stalla, G.
Holsboer, F.
author_facet Arzt, E.
Kovalovsky, D.
Müller Igaz, L.
Costas, M.
Plazas, P.
Refojo, D.
Páez-Pereda, M.
Reul, J.M.H.M.
Stalla, G.
Holsboer, F.
author_sort Arzt, E.
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
url http://hdl.handle.net/20.500.12110/paper_00778923_v917_n_p672_Arzt
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