RU 38486: A potent antiglucocorticoid in vitro and in vivo

Gagne, Didier; Pons, Michel; Philibert, D.

doi:10.1016/0022-4731(85)90401-7

Cited by 172 publications

(101 citation statements)

References 24 publications

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“…2B). In addition, the antiglucocorticoid agent RU 486 [35) almost completely antagonizes the effect of a maximally efficient dose of dexamethasone. Similarly, IL-6-induced transcriptional activity depends on the concentration of the effector with half-maximal and maximal effects observed with 10-20U/ml and 250-500 U/ml, respectively (Fig.…”

Section: Resultsmentioning

confidence: 97%

Regulation of Expression of the Rat Serine Protease Inhibitor 2.3 Gene by Glucocorticoids and Interleukin‐6

Simar‐Blanchet

Paul

Mercier

et al. 1996

European Journal of Biochemistry

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The rat serine protease inhibitor 2.3 gene (spi 2.3) is almost completely silent in normal animals and is transiently expressed during acute inflammation. It encodes a potential anti-elastase which is likely to play a major physiological role for the host defense. Two well-known inflammatory mediators, glucocorticoids and interleukin-6 (IL-6) activate the spi 2.3 promoter and increase steady-state levels of mRNA in cultured hepatocytes. GC activation is mediated by a single glucocorticoid-response element which seems to act autonomously. A unique array of four functional IL-6-response sites was identified in the spi 2.3 promoter. Three of them (C-IT-1V) bear structural identity to the CCAAT/enhancer-binding-protein-binding site consensus sequence, whereas the forth closely resembles the consensus KB nuclear factor recognition motif. The C-IV element, which is the most active, contains the motif 5'-CTGGGA and binds the IL-6-inducible acute-phase response factor present in liver nuclear extracts from inflamed rats. Both basal and IL-6-dependent activities of each individual cytokine-response element tcsted separately are strongly down regulated by a recently identified regulatory sequence [Le Cam, A. & Legraverend, C. (1995) Eur: J. Biochem. 231, 620-6271, located in the 3' untranslated region of the spi 2.3 gene. However, this repressor element does not significantly affect overall IL-6-dependent spi 2.3 promoter activity. This suggests that, in the context of the active gene in vivo, all four IL-6-response sites, which are largely redundant, cooperate to overcome the strong repressive effect of the 3' untranslated region silencer and are needed to bring about a maximal TL-6 response.These data reveal a novel type of regulation of an acute-phase gene involving different classes of IL-6-response elements controlled by a repressor and acting in conjunction with a glucocorticoid-response element.

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Section: Resultsmentioning

confidence: 97%

Regulation of Expression of the Rat Serine Protease Inhibitor 2.3 Gene by Glucocorticoids and Interleukin‐6

Simar‐Blanchet

Paul

Mercier

et al. 1996

European Journal of Biochemistry

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“…Commercially available drugs can reduce systemic exposure and toxicity of ingested toxins (Seneca et al 2010). Likewise, the physiological stress response can be suppressed (Gagne et al 1985) or elevated (Muller et al 2009). …”

Section: Future Research Directionsmentioning

confidence: 99%

The dilemma of foraging herbivores: dealing with food and fear

et al. 2014

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“…However, all of these potent glucocorticoid analogues still displayed appreciable affinity towards MRs, which hampered the discrimination between MR-and GR-mediated events. In the beginning of the 1980s a new class of selective GR agonists and antagonists became available, which turned out to be very instrumental in quantifying MRs and GRs independently and in studying MR-and GR-mediated effects independently (Philibert and Moguilevski, 1983;Philibert, 1984;Gagne et al, 1985). This new class of analogues includes the synthetic glucocorticoid agonist RU 28362 and the mixed glucocorticoid and progesterone antagonist RU 38486 (see Fig.…”

Section: Mineralocorticoid and Glu~ic~rticoid Receptors In The Brainmentioning

confidence: 99%

Mineralocorticoid and glucocorticoid receptors in the brain. Implications for ion permeability and transmitter systems

Joëls

Kloet

1994

Progress in Neurobiology

368

168

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RU 38486: A potent antiglucocorticoid in vitro and in vivo

Cited by 172 publications

References 24 publications

Regulation of Expression of the Rat Serine Protease Inhibitor 2.3 Gene by Glucocorticoids and Interleukin‐6

Regulation of Expression of the Rat Serine Protease Inhibitor 2.3 Gene by Glucocorticoids and Interleukin‐6

The dilemma of foraging herbivores: dealing with food and fear

Mineralocorticoid and glucocorticoid receptors in the brain. Implications for ion permeability and transmitter systems

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