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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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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.
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.
Chicago author-date
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.
Chicago author-date (all authors)
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.
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.
IEEE
[1]
K. De Bosscher, M. L. Schmitz, W. Vanden Berghe, S. Plaisance, W. Fiers, and G. Haegeman, “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, vol. 94, no. 25, pp. 13504–13509, 1997.
@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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