Molecular and functional evidence for in vitro cytokine enhancement of human and murine target cell sensitivity to glucocorticoids: TNF-α priming increases glucocorticoid inhibition of TNF-α-induced cytotoxicity/apoptosis

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Cytokine-induced glucocorticoid secretion and glucocorticoid inhibition of cytokine synthesis and pleiotropic actions act as important safeguards in preventing cytokine overreaction. We found that TNF-α increased glucocorticoid-induced transcriptional activity of the glucocorticoid receptor (GR) via...

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Autores principales: Costas, M., Trapp, T., Pereda, M.P., Sauer, J., Rupprecht, R., Nahmod, V.E., Reul, J.M.H.M., Holsboer, F., Arzt, E.
Formato: Artículo publishedVersion
Publicado: 1996
Materias:
apoptosis
cytokines
glucocorticoid receptor
glucocorticoid response element
TNF-α
glucocorticoid
tumor necrosis factor alpha
animal cell
article
cytotoxicity
human
human cell
immune response
immunoregulation
mouse
nonhuman
priority journal
target cell
transcription regulation
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_00219738_v98_n6_p1409_Costas
http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_00219738_v98_n6_p1409_Costas_oai
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Repositorio Digital de la Universidad de Buenos Aires (UBA) de Universidad de Buenos Aires
id I28-R145-paper_00219738_v98_n6_p1409_Costas_oai
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spelling I28-R145-paper_00219738_v98_n6_p1409_Costas_oai2020-10-19 Costas, M. Trapp, T. Pereda, M.P. Sauer, J. Rupprecht, R. Nahmod, V.E. Reul, J.M.H.M. Holsboer, F. Arzt, E. 1996 Cytokine-induced glucocorticoid secretion and glucocorticoid inhibition of cytokine synthesis and pleiotropic actions act as important safeguards in preventing cytokine overreaction. We found that TNF-α increased glucocorticoid-induced transcriptional activity of the glucocorticoid receptor (GR) via the glucocorticoid response elements (GRE) in L-929 mouse fibroblasts transfected with a glucocorticoid-inducible reporter plasmid. In addition, TNF-α also enhanced GR number. The TNF-α effect on transcriptional activity was absent in other cell lines that express TNF-α receptors but not GRs, and became manifest when a GR expression vector was cotransfected, indicating that TNF-α, independent of any effect it may have on GR number, has a stimulatory effect on the glucocorticoid-induced transcriptional activity of the GR. Moreover, TNF-α increased GR binding to GRE. As a functional biological correlate of this mechanism, priming of L- 929 cells with a low (noncytotoxic) dose of TNF-α significantly increased the sensitivity to glucocorticoid inhibition of TNF-α-induced cytotoxicity/apoptosis. TNF-α and IL-1β had the same stimulatory action on glucocorticoid-induced transcriptional activity of the GR via the GRE, in different types of cytokine/glucocorticoid target cells (glioma, pituitary, epithelioid). The phenomenon may therefore reflect a general molecular mechanism whereby cytokines modulate the transcriptional activity of the GR, thus potentiating the counterregulation by glucocorticoids at the level of their target cells. Fil:Costas, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Pereda, M.P. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. application/pdf http://hdl.handle.net/20.500.12110/paper_00219738_v98_n6_p1409_Costas info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar J. CLIN. INVEST. 1996;98(6):1409-1416 apoptosis cytokines glucocorticoid receptor glucocorticoid response element TNF-α glucocorticoid tumor necrosis factor alpha animal cell apoptosis article cytotoxicity human human cell immune response immunoregulation mouse nonhuman priority journal target cell transcription regulation Molecular and functional evidence for in vitro cytokine enhancement of human and murine target cell sensitivity to glucocorticoids: TNF-α priming increases glucocorticoid inhibition of TNF-α-induced cytotoxicity/apoptosis info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_00219738_v98_n6_p1409_Costas_oai
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-145
collection Repositorio Digital de la Universidad de Buenos Aires (UBA)
topic apoptosis
cytokines
glucocorticoid receptor
glucocorticoid response element
TNF-α
glucocorticoid
tumor necrosis factor alpha
animal cell
apoptosis
article
cytotoxicity
human
human cell
immune response
immunoregulation
mouse
nonhuman
priority journal
target cell
transcription regulation
spellingShingle apoptosis
cytokines
glucocorticoid receptor
glucocorticoid response element
TNF-α
glucocorticoid
tumor necrosis factor alpha
animal cell
apoptosis
article
cytotoxicity
human
human cell
immune response
immunoregulation
mouse
nonhuman
priority journal
target cell
transcription regulation
Costas, M.
Trapp, T.
Pereda, M.P.
Sauer, J.
Rupprecht, R.
Nahmod, V.E.
Reul, J.M.H.M.
Holsboer, F.
Arzt, E.
Molecular and functional evidence for in vitro cytokine enhancement of human and murine target cell sensitivity to glucocorticoids: TNF-α priming increases glucocorticoid inhibition of TNF-α-induced cytotoxicity/apoptosis
topic_facet apoptosis
cytokines
glucocorticoid receptor
glucocorticoid response element
TNF-α
glucocorticoid
tumor necrosis factor alpha
animal cell
apoptosis
article
cytotoxicity
human
human cell
immune response
immunoregulation
mouse
nonhuman
priority journal
target cell
transcription regulation
description Cytokine-induced glucocorticoid secretion and glucocorticoid inhibition of cytokine synthesis and pleiotropic actions act as important safeguards in preventing cytokine overreaction. We found that TNF-α increased glucocorticoid-induced transcriptional activity of the glucocorticoid receptor (GR) via the glucocorticoid response elements (GRE) in L-929 mouse fibroblasts transfected with a glucocorticoid-inducible reporter plasmid. In addition, TNF-α also enhanced GR number. The TNF-α effect on transcriptional activity was absent in other cell lines that express TNF-α receptors but not GRs, and became manifest when a GR expression vector was cotransfected, indicating that TNF-α, independent of any effect it may have on GR number, has a stimulatory effect on the glucocorticoid-induced transcriptional activity of the GR. Moreover, TNF-α increased GR binding to GRE. As a functional biological correlate of this mechanism, priming of L- 929 cells with a low (noncytotoxic) dose of TNF-α significantly increased the sensitivity to glucocorticoid inhibition of TNF-α-induced cytotoxicity/apoptosis. TNF-α and IL-1β had the same stimulatory action on glucocorticoid-induced transcriptional activity of the GR via the GRE, in different types of cytokine/glucocorticoid target cells (glioma, pituitary, epithelioid). The phenomenon may therefore reflect a general molecular mechanism whereby cytokines modulate the transcriptional activity of the GR, thus potentiating the counterregulation by glucocorticoids at the level of their target cells.
format Artículo
Artículo
publishedVersion
author Costas, M.
Trapp, T.
Pereda, M.P.
Sauer, J.
Rupprecht, R.
Nahmod, V.E.
Reul, J.M.H.M.
Holsboer, F.
Arzt, E.
author_facet Costas, M.
Trapp, T.
Pereda, M.P.
Sauer, J.
Rupprecht, R.
Nahmod, V.E.
Reul, J.M.H.M.
Holsboer, F.
Arzt, E.
author_sort Costas, M.
title Molecular and functional evidence for in vitro cytokine enhancement of human and murine target cell sensitivity to glucocorticoids: TNF-α priming increases glucocorticoid inhibition of TNF-α-induced cytotoxicity/apoptosis
title_short Molecular and functional evidence for in vitro cytokine enhancement of human and murine target cell sensitivity to glucocorticoids: TNF-α priming increases glucocorticoid inhibition of TNF-α-induced cytotoxicity/apoptosis
title_full Molecular and functional evidence for in vitro cytokine enhancement of human and murine target cell sensitivity to glucocorticoids: TNF-α priming increases glucocorticoid inhibition of TNF-α-induced cytotoxicity/apoptosis
title_fullStr Molecular and functional evidence for in vitro cytokine enhancement of human and murine target cell sensitivity to glucocorticoids: TNF-α priming increases glucocorticoid inhibition of TNF-α-induced cytotoxicity/apoptosis
title_full_unstemmed Molecular and functional evidence for in vitro cytokine enhancement of human and murine target cell sensitivity to glucocorticoids: TNF-α priming increases glucocorticoid inhibition of TNF-α-induced cytotoxicity/apoptosis
title_sort molecular and functional evidence for in vitro cytokine enhancement of human and murine target cell sensitivity to glucocorticoids: tnf-α priming increases glucocorticoid inhibition of tnf-α-induced cytotoxicity/apoptosis
publishDate 1996
url http://hdl.handle.net/20.500.12110/paper_00219738_v98_n6_p1409_Costas
http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_00219738_v98_n6_p1409_Costas_oai
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_version_ 1766026577413406720

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