RETRACTED: Ligand‐induced differentiation of glucocorticoid receptor (GR) trans‐repression and transactivation: preferential targetting of NF‐ κ B and lack of I‐ κ B involvement

Abstract

1 Glucocorticoids are highly e ective in controlling chronic in¯ammatory diseases, such as asthma and rheumatoid arthritis, but the exact molecular mechanism of their anti-in¯ammatory action remains uncertain. They act by binding to a cytosolic receptor (GR) resulting in activation or repression of gene expression. This may occur via direct binding of the GR to DNA (transactivation) or by inhibition of the activity of transcription factors such as AP-1 and NF-kB (transrepression). to inhibit a 36kB was associated with inhibition of GM-CSF release. 5 These data suggest that the anti-in¯ammatory properties of a range of glucocorticoids relate to their ability to transrepress rather than transactivate genes.

Exacerbation of CNS inflammation and neurodegeneration by systemic LPS treatment is independent of circulating IL-1β and IL-6

“…This indicates that the pro-drug dexamethasone-21-phosphate has been converted to the active metabolite dexamethasone and has effected inhibition. Though the mechanisms of this inhibition are still controversial, it is widely accepted that dexamethasone can block NFκB-dependent gene transcription by direct transrepression [ 27 ] and the inhibition of cytokine synthesis observed in the current study is entirely consistent with this idea. However, the intact CNS transcription of cytokine genes that are also NFκB-dependent indicates that dexamethasone is either not effective in the CNS, or does not reach the CNS at sufficient concentrations to effect any inhibition of these processes.…”

Exacerbation of CNS inflammation and neurodegeneration by systemic LPS treatment is independent of circulating IL-1β and IL-6

“…This indicates that the pro-drug dexamethasone-21-phosphate has been converted to the active metabolite dexamethasone and has effected inhibition. Though the mechanisms of this inhibition are still controversial, it is widely accepted that dexamethasone can block NFκB-dependent gene transcription by direct transrepression [ 27 ] and the inhibition of cytokine synthesis observed in the current study is entirely consistent with this idea. However, the intact CNS transcription of cytokine genes that are also NFκB-dependent indicates that dexamethasone is either not effective in the CNS, or does not reach the CNS at sufficient concentrations to effect any inhibition of these processes.…”

The Injectable-Only Contraceptive Medroxyprogesterone Acetate, Unlike Norethisterone Acetate and Progesterone, Regulates Inflammatory Genes in Endocervical Cells via the Glucocorticoid Receptor

“…MPA, unlike NET-A and P4, increases mRNA expression of the anti-inflammatory genes GILZ and IκBα, in both the cervical epithelial cells lines. Interestingly, this differential regulation of IκBα mRNA is not mimicked by IκBα protein levels, suggesting that GR-mediated increase in IκBα protein levels does not play a major role in regulation of IL-6, IL-8 and RANTES genes in these cells, consistent with reports for some cells but not others [68]–[72]. MPA unlike NET-A, decreases expression of the pro-inflammatory IL-6, IL-8 and RANTES genes in the endocervical epithelial cell line, as well as IL-6 and IL-8 in the HeLa cell line.…”

A One-Arm Homologous Recombination Approach for Developing Nuclear Receptor Assays in Somatic Cells

“…RU486 (also known as mifepristone), a well known partial antagonist of GR, 11 was used to validate this cell line pharmacologically. Consistent with previous reports, 12,13 RU486 inhibited the stimulatory effect of dexamethasone with an IC 50 of 1 nM (Fig. 3C).…”

Exacerbation of CNS inflammation and neurodegeneration by systemic LPS treatment is independent of circulating IL-1β and IL-6

“…This indicates that the pro-drug dexamethasone-21-phosphate has been converted to the active metabolite dexamethasone and has effected inhibition. Though the mechanisms of this inhibition are still controversial, it is widely accepted that dexamethasone can block NFκB-dependent gene transcription by direct transrepression [ 27 ] and the inhibition of cytokine synthesis observed in the current study is entirely consistent with this idea. However, the intact CNS transcription of cytokine genes that are also NFκB-dependent indicates that dexamethasone is either not effective in the CNS, or does not reach the CNS at sufficient concentrations to effect any inhibition of these processes.…”

The Injectable-Only Contraceptive Medroxyprogesterone Acetate, Unlike Norethisterone Acetate and Progesterone, Regulates Inflammatory Genes in Endocervical Cells via the Glucocorticoid Receptor

“…MPA, unlike NET-A and P4, increases mRNA expression of the anti-inflammatory genes GILZ and IκBα, in both the cervical epithelial cells lines. Interestingly, this differential regulation of IκBα mRNA is not mimicked by IκBα protein levels, suggesting that GR-mediated increase in IκBα protein levels does not play a major role in regulation of IL-6, IL-8 and RANTES genes in these cells, consistent with reports for some cells but not others [68]–[72]. MPA unlike NET-A, decreases expression of the pro-inflammatory IL-6, IL-8 and RANTES genes in the endocervical epithelial cell line, as well as IL-6 and IL-8 in the HeLa cell line.…”

A One-Arm Homologous Recombination Approach for Developing Nuclear Receptor Assays in Somatic Cells

“…RU486 (also known as mifepristone), a well known partial antagonist of GR, 11 was used to validate this cell line pharmacologically. Consistent with previous reports, 12,13 RU486 inhibited the stimulatory effect of dexamethasone with an IC 50 of 1 nM (Fig. 3C).…”

Exacerbation of CNS inflammation and neurodegeneration by systemic LPS treatment is independent of circulating IL-1β and IL-6

“…This indicates that the pro-drug dexamethasone-21-phosphate has been converted to the active metabolite dexamethasone and has effected inhibition. Though the mechanisms of this inhibition are still controversial, it is widely accepted that dexamethasone can block NFκB-dependent gene transcription by direct transrepression [ 27 ] and the inhibition of cytokine synthesis observed in the current study is entirely consistent with this idea. However, the intact CNS transcription of cytokine genes that are also NFκB-dependent indicates that dexamethasone is either not effective in the CNS, or does not reach the CNS at sufficient concentrations to effect any inhibition of these processes.…”

The Injectable-Only Contraceptive Medroxyprogesterone Acetate, Unlike Norethisterone Acetate and Progesterone, Regulates Inflammatory Genes in Endocervical Cells via the Glucocorticoid Receptor

“…MPA, unlike NET-A and P4, increases mRNA expression of the anti-inflammatory genes GILZ and IκBα, in both the cervical epithelial cells lines. Interestingly, this differential regulation of IκBα mRNA is not mimicked by IκBα protein levels, suggesting that GR-mediated increase in IκBα protein levels does not play a major role in regulation of IL-6, IL-8 and RANTES genes in these cells, consistent with reports for some cells but not others [68]–[72]. MPA unlike NET-A, decreases expression of the pro-inflammatory IL-6, IL-8 and RANTES genes in the endocervical epithelial cell line, as well as IL-6 and IL-8 in the HeLa cell line.…”

A One-Arm Homologous Recombination Approach for Developing Nuclear Receptor Assays in Somatic Cells

“…RU486 (also known as mifepristone), a well known partial antagonist of GR, 11 was used to validate this cell line pharmacologically. Consistent with previous reports, 12,13 RU486 inhibited the stimulatory effect of dexamethasone with an IC 50 of 1 nM (Fig. 3C).…”