Abstract:
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.
Registro:
Documento: |
Artículo
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Título: | 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 |
Autor: | Costas, M.; Trapp, T.; Pereda, M.P.; Sauer, J.; Rupprecht, R.; Nahmod, V.E.; Reul, J.M.H.M.; Holsboer, F.; Arzt, E. |
Filiación: | Inst. de Invest. Médicas, Universidad de Buenos Aires, 1427 Buenos Aires, Argentina Departamento de Biología-FCEN, Universidad de Buenos Aires, Argentine National Research Council, 1427 Buenos Aires, Argentina Max-Planck-Institute of Psychiatry, Clinical Institute, 80804 Munich, Germany Inst. de Invest. Médicas, Donato Alvarez 3150, 1427 Buenos Aires, Argentina
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Palabras clave: | 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 |
Año: | 1996
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Volumen: | 98
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Número: | 6
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Página de inicio: | 1409
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Página de fin: | 1416
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DOI: |
http://dx.doi.org/10.1172/JCI118928 |
Título revista: | Journal of Clinical Investigation
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Título revista abreviado: | J. CLIN. INVEST.
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ISSN: | 00219738
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CODEN: | JCINA
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PDF: | https://bibliotecadigital.exactas.uba.ar/download/paper/paper_00219738_v98_n6_p1409_Costas.pdf |
Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219738_v98_n6_p1409_Costas |
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Citas:
---------- APA ----------
Costas, M., Trapp, T., Pereda, M.P., Sauer, J., Rupprecht, R., Nahmod, V.E., Reul, J.M.H.M.,..., Arzt, E.
(1996)
. 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. Journal of Clinical Investigation, 98(6), 1409-1416.
http://dx.doi.org/10.1172/JCI118928---------- CHICAGO ----------
Costas, M., Trapp, T., Pereda, M.P., Sauer, J., Rupprecht, R., Nahmod, V.E., et al.
"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"
. Journal of Clinical Investigation 98, no. 6
(1996) : 1409-1416.
http://dx.doi.org/10.1172/JCI118928---------- MLA ----------
Costas, M., Trapp, T., Pereda, M.P., Sauer, J., Rupprecht, R., Nahmod, V.E., et al.
"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"
. Journal of Clinical Investigation, vol. 98, no. 6, 1996, pp. 1409-1416.
http://dx.doi.org/10.1172/JCI118928---------- VANCOUVER ----------
Costas, M., Trapp, T., Pereda, M.P., Sauer, J., Rupprecht, R., Nahmod, V.E., et al. 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. J. CLIN. INVEST. 1996;98(6):1409-1416.
http://dx.doi.org/10.1172/JCI118928