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Glucocorticoid-mediated repression of nuclear factor-κB-dependent transcription involves direct interference with transactivation

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Abstract
Glucocorticoids exert multiple anti-inflammatory activities, one of which is the inhibition of transcription dependent on the nuclear Factor (NP)-kappa B, It has been suggested that the effect of dexamethasone (DEX), a glucocorticoid analog, is attributed to an increased production of the inhibitory I kappa B molecule, which in turn would hind and remove activated, DNA-bound NF-kappa B complexes in the cell nucleus. Upon investigating DEX-mediated repression of interleukin-6 expression induced by tumor necrosis factor, DEX treatment was found to act directly on NF-kappa B-dependent transcription, without changing the expression level of I kappa B. Neither the mRNA of I kappa B nor the protein was significantly elevated by a combined treatment with tumor necrosis factor and DEX of murine endothelial or fibroblast cells, The DNA-binding activity of induced NF-kappa B also remained unchanged after stimulation of cells with DES. Evidence for a direct nuclear mechanism of action was obtained by analysis of cell lines stably expressing a fusion protein between the DNA-binding domain of the It-east Gall protein and the transactivating p65 subunit of NF-kappa B, Expression of a Gal-1-dependent luciferase reporter gent activated by this nuclear fusion protein was also strongly repressed after addition of DEX. Because the DNA-binding activity elf the Gal-1 fusion protein was not affected by DEX, it tan be concluded that the reduction of gene activation was caused by interference of the activated. glucocorticoid receptor with the Irans;activation potential of the Nf-kappa B p65 subunit.
Keywords
INTERLEUKIN-6 GENE-EXPRESSION, TUMOR-NECROSIS-FACTOR, CELL-LINES, NEGATIVE REGULATION, HUMAN-FIBROBLASTS, P65 SUBUNIT, RECEPTOR, ACTIVATION, PROTEIN, DNA

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Chicago
De Bosscher, Karolien, M Lienhard Schmitz, Wim Vanden Berghe, Stéphane Plaisance, Walter Fiers, and Guy Haegeman. 1997. “Glucocorticoid-mediated Repression of Nuclear factor-κB-dependent Transcription Involves Direct Interference with Transactivation.” Proceedings of the National Academy of Sciences of the United States of America 94 (25): 13504–13509.
APA
De Bosscher, K., Schmitz, M. L., Vanden Berghe, W., Plaisance, S., Fiers, W., & Haegeman, G. (1997). Glucocorticoid-mediated repression of nuclear factor-κB-dependent transcription involves direct interference with transactivation. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 94(25), 13504–13509.
Vancouver
1.
De Bosscher K, Schmitz ML, Vanden Berghe W, Plaisance S, Fiers W, Haegeman G. Glucocorticoid-mediated repression of nuclear factor-κB-dependent transcription involves direct interference with transactivation. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 1997;94(25):13504–9.
MLA
De Bosscher, Karolien, M Lienhard Schmitz, Wim Vanden Berghe, et al. “Glucocorticoid-mediated Repression of Nuclear factor-κB-dependent Transcription Involves Direct Interference with Transactivation.” PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 94.25 (1997): 13504–13509. Print.
@article{186199,
  abstract     = {Glucocorticoids exert multiple anti-inflammatory activities, one of which is the inhibition of transcription dependent on the nuclear Factor (NP)-kappa B, It has been suggested that the effect of dexamethasone (DEX), a glucocorticoid analog, is attributed to an increased production of the inhibitory I kappa B molecule, which in turn would hind and remove activated, DNA-bound NF-kappa B complexes in the cell nucleus. Upon investigating DEX-mediated repression of interleukin-6 expression induced by tumor necrosis factor, DEX treatment was found to act directly on NF-kappa B-dependent transcription, without changing the expression level of I kappa B. Neither the mRNA of I kappa B nor the protein was significantly elevated by a combined treatment with tumor necrosis factor and DEX of murine endothelial or fibroblast cells, The DNA-binding activity of induced NF-kappa B also remained unchanged after stimulation of cells with DES. Evidence for a direct nuclear mechanism of action was obtained by analysis of cell lines stably expressing a fusion protein between the DNA-binding domain of the It-east Gall protein and the transactivating p65 subunit of NF-kappa B, Expression of a Gal-1-dependent luciferase reporter gent activated by this nuclear fusion protein was also strongly repressed after addition of DEX. Because the DNA-binding activity elf the Gal-1 fusion protein was not affected by DEX, it tan be concluded that the reduction of gene activation was caused by interference of the activated. glucocorticoid receptor with the Irans;activation potential of the Nf-kappa B p65 subunit.},
  author       = {De Bosscher, Karolien and Schmitz, M Lienhard and Vanden Berghe, Wim and Plaisance, Stéphane and Fiers, Walter and Haegeman, Guy},
  issn         = {0027-8424},
  journal      = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
  keywords     = {INTERLEUKIN-6 GENE-EXPRESSION,TUMOR-NECROSIS-FACTOR,CELL-LINES,NEGATIVE REGULATION,HUMAN-FIBROBLASTS,P65 SUBUNIT,RECEPTOR,ACTIVATION,PROTEIN,DNA},
  language     = {eng},
  number       = {25},
  pages        = {13504--13509},
  title        = {Glucocorticoid-mediated repression of nuclear factor-κB-dependent transcription involves direct interference with transactivation},
  url          = {http://dx.doi.org/10.1073/pnas.94.25.13504},
  volume       = {94},
  year         = {1997},
}

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